prompt_front: Now, answer the following question based on the text below, only give me the answer and do not output any other words.

Question: Can individual molecules of indeno[1,2-a]fluorene switch between open-shell and closed-shell states?

Read the following text and answer briefly.

Context 1: Paper Info

Title: Bistability between π-diradical open-shell and closed-shell states in indeno[1,2-a]fluorene
Publish Date: Unkown
Author List: Shantanu Mishra (from IBM Research Europe -Zurich), Manuel Vilas-Varela (from Department of Organic Chemistry, Center for Research in Biological Chemistry and Molecular Materials (CiQUS), University of Santiago de Compostela), Leonard-Alexander Lieske (from IBM Research Europe -Zurich), Ricardo Ortiz (from Donostia International Physics Center (DIPC)), Igor Rončević (from Department of Chemistry, University of Oxford), Florian Albrecht (from IBM Research Europe -Zurich), Diego Peña (from Department of Organic Chemistry, Center for Research in Biological Chemistry and Molecular Materials (CiQUS), University of Santiago de Compostela), Leo Gross (from IBM Research Europe -Zurich)

Figure

Fig  1 | Non-benzenoid non-alternant polycyclic conjugated hydrocarbons a, Classical nonbenzenoid non-alternant polycyclic conjugated hydrocarbons: pentalene, azulene and heptalene b, Generation of indacenes and indenoindenes through benzinterposition and benzannelation of pentalene, respectively Gray filled rings represent Clar sextets c, Closed-shell Kekulé (left) and openshell non-Kekulé (right) resonance structures of QDMs Note that meta-QDM is a non-Kekulé molecule All indenofluorene isomers, being derived through benzannelation of indacenes, contain a central QDM moiety d, Closed-shell Kekulé (top) and open-shell non-Kekulé (bottom) resonance structures of indenofluorenes Compared to their closed-shell structures, 1 and 5 gain two Clar sextets in the openshell structure, while 2-4 gain only one Clar sextet in the open-shell structure Colored bonds in d highlight the ortho-and para-QDM moieties in the two closed-shell Kekulé structures of 5  e, Scheme of on-surface generation of 5 by voltage pulse-induced dehydrogenation of 6 (C20H14) Structures 7 and 8 represent the two monoradical species (C20H13) 
Fig  2 | Characterization of open-shell indeno[1,2-a]fluorene on bilayer NaCl/Au(111) a, DFTcalculated wave functions of the frontier orbitals of 5OS in the triplet configuration for the spin up (occupied) level (isovalue: 0 002 e -Å -3 ) Blue and red colors represent opposite phases of the wave function b, Corresponding DFT-calculated spin density of 5OS (isovalue: 0 01 e -Å -3) Blue and orange colors represent spin up and spin down densities, respectively c, Probability density of the SOMOs of 5OS (isovalue: 0 001 e -Å -3 ) d, DFT-calculated bond lengths of 5OS e, Constant-height I(V) spectra acquired on a species of 5 assigned as 5OS, along with the corresponding dI/dV(V) spectra Open feedback parameters: V = -2 V, I = 0 17 pA (negative bias side) and V = 2 V, I = 0 17 pA (positive bias side) Acquisition position of the spectra is shown in Supplementary Fig 7 f, Scheme of many-body transitions associated to the measured ionic resonances of 5OS Also shown are STM images of assigned 5OS at biases where the corresponding transitions become accessible Scanning parameters: I = 0 3 pA (V = -1 2V and -1 5 V) and 0 2 pA (V = 1 3 V and 1 6 V)  g, Laplace-filtered AFM image of assigned 5OS STM set point: V = 0 2 V, I = 0 5 pA on bilayer NaCl, Δz = -0 3Å The tip-height offset Δz for each panel is provided with respect to the STM setpoint, and positive (negative) values of Δz denote tip approach (retraction) from the STM setpoint f and g show the same molecule at the same adsorption site, which is next to a trilayer NaCl island The bright and dark features in the trilayer NaCl island in g correspond to Cl -and Na + ions, respectively Scale bars: 10 Å (f) and 5 Å (g) 
Fig  3 | Characterization of closed-shell indeno[1,2-a]fluorene on bilayer NaCl/Au(111) a, DFTcalculated wave functions of the frontier orbitals of closed-shell 5 0 (isovalue: 0 002 e -Å -3 ) The wave functions shown here are calculated for the 5para geometry b, DFT-calculated bond lengths of 5ortho (top) and 5para (bottom) c, Constant-height I(V) spectra acquired on a species of 5 assigned as 5para, along with the corresponding dI/dV(V) spectra Open feedback parameters: V = -2 V, I = 0 15 pA (negative bias side) and V = 2 2 V, I = 0 15 pA (positive bias side) Acquisition position of the spectra is shown in Supplementary Fig  7  d, Scheme of many-body transitions associated to the measured ionic resonances of 5para Also shown are STM images of assigned 5para at biases where the corresponding transitions become accessible Scanning parameters: I = 0 15 pA (V = -1 5 V) and 0 2 pA (V = 1 7 V)  e, Laplace-filtered AFM image of assigned 5para STM set point: V = 0 2 V, I = 0 5 pA on bilayer NaCl, Δz = -0 7 Å  f, Selected bonds labeled for highlighting bond order differences between 5para and 5ortho For the bond pairs a/b, c/d and e/f, the bonds labeled in bold exhibit a higher bond order than their neighboring labeled bonds in 5para g, Laplace-filtered AFM images of 5 on bilayer NaCl/Cu(111) showing switching between 5OS and 5para as the molecule changes its adsorption position The faint protrusion adjacent to 5 is a defect that stabilizes the adsorption of 5  STM set point: V = 0 2 V, I = 0 5 pA on bilayer NaCl, Δz = -0 3Å  STM and STS data in c and d are acquired on the same species, while the AFM data in e is acquired on a different species Scale bars: 10 Å (d) and 5 Å (e,g) 
NMR (300 MHz, CDCl3) δ: 7 51 (m, 2H), 7 40 -7 28 (m, 5H), 7 27 -7 20 (m, 2H), 7 13 (d, J = 7 7 Hz, 1H), 2 07 (s, 3H), 1 77 (s, 3H) ppm  13C NMR-DEPT (75 MHz, CDCl3, 1:1 mixture of atropisomers) δ: 141 2 (C), 141 1 (C), 140 0 (C), 139 4 (2C), 137 5 (C), 137 4 (C), 136 0 (3C), 134 8 (C), 134 5 (C), 134 1 (C), 134 0 (C), 133 7 (C), 133 6 (C), 131 6 (CH), 131 2 (CH), 131 1 (CH), 130 7 (CH), 129 8 (CH), 129 7 (CH), 129 5 (CH), 129 4 (CH), 129 0 (CH), 128 9 (CH), 128 7 (2CH), 128 6 (2CH), 127 2 (CH), 127 1 (CH), 127 0 (CH), 126 9 (CH), 126 7 (CH), 126 6 (CH), 20 6 (CH3), 20 5 (CH3), 17 7 (CH3), 17 5 (CH3) ppm MS (APCI) m/z (%): 327 (M+1, 100) HRMS: C20H16Cl2; calculated: 327 0702, found: 327 0709 
NMR (500 MHz, CDCl3) δ: 7 93 (d, J = 7 6 Hz, 1H), 7 85 (d, J = 7 5 Hz, 1H), 7 78 (d, J = 7 7 Hz, 1H), 7 65 (d, J = 7 4 Hz, 1H), 7 61 (d, J = 7 5 Hz, 1H), 7 59 (d, J = 7 7 Hz, 1H), 7 47 (ddd, J = 8 4, 7 2, 1 1 Hz, 1H), 7 42 (dd, J = 8 1, 7 0 Hz, 1H), 7 35 (m, 2H), 4 22 (s, 3H), 4 02 (s, 3H) ppm  13C NMR-DEPT (125 MHz, CDCl3) δ: 144 1 (C), 143 3 (C), 142 3 (C), 141 9 (C), 141 8 (C), 141 2 (C), 138 2 (C), 136 5 (C), 127 0 (CH), 126 9 (CH), 126 7 (CH), 126 6 (CH), 125 3 (CH), 125 2 (CH), 123 6 (CH), 122 2 (CH), 119 9 (CH), 118 4 (CH), 37 4 (CH2), 36 3 (CH2) ppm MS (APCI) m/z (%): 254 (M+, 88) HRMS: C20H14; calculated: 254 1090, found: 254 1090 

abstract

Indenofluorenes are non-benzenoid conjugated hydrocarbons that have received great interest owing to their unusual electronic structure and potential applications in nonlinear optics and photovoltaics  Here, we report the generation of unsubstituted indeno[1,2-a]fluorene, the final and yet unreported parent indenofluorene regioisomer, on various surfaces by cleavage of two C-H bonds in 7,12-dihydro indeno[1,2-a]fluorene through voltage pulses applied by the tip of a combined scanning tunneling microscope and atomic force microscope 
On bilayer NaCl on Au(111), indeno[1,2a]fluorene is in the neutral charge state, while it exhibits charge bistability between neutral and anionic states on the lower work function surfaces of bilayer NaCl on Ag(111) and Cu(111)  In the neutral state, indeno[1,2-a]fluorene exhibits either of two ground states: an open-shell π-diradical state, predicted to be a triplet by density functional and multireference many-body perturbation theory calculations, or a closedshell state with a para-quinodimethane moiety in the as-indacene core 
Switching between open-and closed-shell states of a single molecule is observed by changing its adsorption site on NaCl  The inclusion of non-benzenoid carbocyclic rings is a viable route to tune the physicochemical properties of polycyclic conjugated hydrocarbons (PCHs)   Non-benzenoid polycycles may lead to local changes in strain, conjugation, aromaticity, and, relevant to the context of the present work, induce an open-shell ground state of the corresponding PCHs  
Many nonbenzenoid PCHs are also non-alternant, where the presence of odd-membered polycycles breaks the bipartite symmetry of the molecular network   Figure shows classical examples of non-benzenoid non-alternant PCHs, namely, pentalene, azulene and heptalene  Whereas azulene is a stable PCH exhibiting Hückel aromaticity ([4n+2] π-electrons, n = 2), pentalene and heptalene are unstable Hückel antiaromatic compounds with [4n] π-electrons, n = 2 (pentalene) and n = 3 (heptalene) 
Benzinterposition of pentalene generates indacenes, consisting of two isomers s-indacene and as-indacene (Fig  )  Apart from being antiaromatic, indacenes also contain proaromatic quinodimethane (QDM) moieties (Fig  ) , which endows them with potential open-shell character  While the parent s-indacene and asindacene have never been isolated, stable derivatives of s-indacene bearing bulky substituents have been synthesized  
A feasible strategy to isolate congeners of otherwise unstable non-benzenoid non-alternant PCHs is through fusion of benzenoid rings at the ends of the π-system, that is, benzannelation  For example, while the parent pentalene is unstable, the benzannelated congener indeno[2,1-a]indene is stable under ambient conditions (Fig  )  
However, the position of benzannelation is crucial for stability: although indeno[2,1a]indene is stable, its regioisomer indeno[1,2-a]indene (Fig  ) oxidizes under ambient conditions   Similarly, benzannelation of indacenes gives rise to the family of PCHs known as indenofluorenes (Fig  ), which constitute the topic of the present work 
Depending on the benzannelation position and the indacene core, five regioisomers can be constructed, namely, indeno [ Practical interest in indenofluorenes stems from their low frontier orbital gap and excellent electrochemical characteristics that render them as useful components in organic electronic devices  
The potential open-shell character of indenofluorenes has led to several theoretical studies on their use as non-linear optical materials and as candidates for singlet fission in organic photovoltaics   Recent theoretical work has also shown that indenofluorene-based ladder polymers may exhibit fractionalized excitations 
Fundamentally, indenofluorenes represent model systems to study the interplay between aromaticity and magnetism at the molecular scale   Motivated by many of these prospects, the last decade has witnessed intensive synthetic efforts toward the realization of indenofluorenes  Derivatives of 1-4 have been realized in solution , while 1-3 have also been synthesized on surfaces and characterized using scanning tunneling microscopy (STM) and atomic force microscopy (AFM), which provide information on molecular orbital densities , molecular structure and oxidation state  
With regards to the open-shell character of indenofluorenes, 2-4 are theoretically and experimentally interpreted to be closed-shell, while calculations indicate that 1 and 5 should exhibit open-shell ground states   Bulk characterization of mesitylsubstituted 1, including X-ray crystallography, temperature-dependent NMR, and electron spin resonance spectroscopy, provided indications of its open-shell ground state  
Electronic characterization of 1 on Au(111) surface using scanning tunneling spectroscopy (STS) revealed a low electronic gap of 0 4 eV (ref  )  However, no experimental proof of an openshell ground state of 1 on Au(111), such as detection of singly occupied molecular orbitals (SOMOs) or spin excitations and correlations due to unpaired electrons , was shown 
In this work, we report the generation and characterization of unsubstituted 5  Our research is motivated by theoretical calculations that indicate 5 to exhibit the largest diradical character among all indenofluorene isomers   The same calculations also predict that 5 should possess a triplet ground state 
Therefore, 5 would qualify as a Kekulé triplet, of which only a handful of examples exist   However, definitive synthesis of 5 has never been reported so far  Previously, Dressler et al  reported transient isolation of mesityl-substituted 5, where it decomposed both in the solution and in solid state , and only the structural proof of the corresponding dianion was obtained 
On-surface generation of a derivative of 5, starting from truxene as a precursor, was recently reported   STM data on this compound, containing the indeno[1,2-a]fluorene moiety as part of a larger PCH, was interpreted to indicate its open-shell ground state  However, the results did not imply the ground state of unsubstituted 5  Here, we show that on insulating surfaces 5 can exhibit either of two ground states: an open-shell or a closed-shell 
We infer the existence of these two ground states based on high-resolution AFM imaging with bond-order discrimination and STM imaging of molecular orbital densities   AFM imaging reveals molecules with two different geometries  Characteristic bond-order differences in the two geometries concur with the geometry of either an open-or a closed-shell state 
Concurrently, STM images at ionic resonances show molecular orbital densities corresponding to SOMOs for the open-shell geometry, but orbital densities of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) for the closed-shell geometry  Our experimental results are in good agreement with density functional theory (DFT) and multireference perturbation theory calculations 
Finally, we observe switching between open-and closed-shell states of a single molecule by changing its adsorption site on the surface  Synthetic strategy toward indeno[1,2-a]fluorene  The generation of 5 relies on the solution-phase synthesis of the precursor 7,12-dihydro indeno[1,2-a]fluorene (6)  Details on synthesis and characterization of 6 are reported in Supplementary Figs 
  Single molecules of 6 are deposited on coinage metal (Au(111), Ag(111) and Cu(111)) or insulator surfaces  In our work, insulating surfaces correspond to two monolayer-thick (denoted as bilayer) NaCl on coinage metal surfaces  Voltage pulses ranging between 4-6 V are applied by the tip of a combined STM/AFM system, which result in cleavage of one C-H bond at each of the pentagonal apices of 6, thereby leading to the generation of 5 (Fig  ) 
In the main text, we focus on the generation and characterization of 5 on insulating surfaces  Generation and characterization of 5 on coinage metal surfaces is shown in Supplementary Fig    )  Blue and orange colors represent spin up and spin down densities, respectively  c, Probability density of the SOMOs of 5OS (isovalue: 0 001 e -Å -3 ) 
d, DFT-calculated bond lengths of 5OS  e, Constant-height I(V) spectra acquired on a species of 5 assigned as 5OS, along with the corresponding dI/dV(V) spectra  Open feedback parameters: V = -2 V, I = 0 17 pA (negative bias side) and V = 2 V, I = 0 17 pA (positive bias side)  Acquisition position of the spectra is shown in Supplementary Fig    f, Scheme of many-body transitions associated to the measured ionic resonances of 5OS 
Also shown are STM images of assigned 5OS at biases where the corresponding transitions become accessible  Scanning parameters: I = 0 3 pA (V = -1 2 V and -1 5 V) and 0 2 pA (V = 1 3 V and 1 6 V)  g, Laplace-filtered AFM image of assigned 5OS  STM set point: V = 0 2 V, I = 0 5 pA on bilayer NaCl, Δz = -0 3
Å  The tip-height offset Δz for each panel is provided with respect to the STM setpoint, and positive (negative) values of Δz denote tip approach (retraction) from the STM setpoint  f and g show the same molecule at the same adsorption site, which is next to a trilayer NaCl island  The bright and dark features in the trilayer NaCl island in g correspond to Cl -and Na + ions, respectively 
Scale bars: 10 Å (f) and 5 Å (g)  To experimentally explore the electronic structure of 5, we used bilayer NaCl films on coinage metal surfaces to electronically decouple the molecule from the metal surfaces  Before presenting the experimental findings, we summarize the results of our theoretical calculations performed on 5 in the neutral charge state (denoted as 5 0 ) 
We start by performing DFT calculations on 5 0 in the gas phase  Geometry optimization performed at the spin-unrestricted UB3LYP/6-31G level of theory leads to one local minimum, 5OS, the geometry of which corresponds to the open-shell resonance structure of 5 (Fig  , the label OS denotes open-shell) 
The triplet electronic configuration of 5OS is the lowest-energy state, with the openshell singlet configuration 90 meV higher in energy  Geometry optimization performed at the restricted closed-shell RB3LYP/6-31G level reveals two local minima, 5para and 5ortho, the geometries of which (Fig  ) exhibit bond length alternations in line with the presence of a para-or an ortho-QDM moiety, respectively, in the as-indacene core of the closed-shell resonance structures of 5 (Fig  )  
Relative to 5OS in the triplet configuration, 5para and 5ortho are 0 40 and 0 43 eV higher in energy, respectively  Additional DFT results are shown in Supplementary Fig    To gain more accurate insights into the theoretical electronic structure of 5, we performed multireference perturbation theory calculations (Supplementary Fig  ) based on quasi-degenerate second-order n-electron valence state perturbation theory (QD-NEVPT2) 
In so far as the order of the ground and excited states are concerned, the results of QD-NEVPT2 calculations qualitatively match with DFT calculations  For 5OS, the triplet configuration remains the lowest-energy state, with the open-shell singlet configuration 60 meV higher in energy  The energy differences between the open-and closed-shell states are substantially reduced in QD-NEVPT2 calculations, with 5para and 5ortho only 0 11 and 0 21 eV higher in energy, respectively, compared to 5OS in the triplet configuration 
We also performed nucleus-independent chemical shift calculations to probe local aromaticity of 5 in the openand closed-shell states  While 5OS in the triplet configuration exhibits local aromaticity at the terminal benzenoid rings, 5OS in the open-shell singlet configuration, 5para and 5ortho all display antiaromaticity (Supplementary Fig  ) 
The choice of the insulating surface determines the charge state of 5: while 5 adopts neutral charge state on the high work function bilayer NaCl/Au(111) surface (irrespective of its openor closed-shell state, Supplementary Fig  ), 5 exhibits charge bistability between 5 0 and the anionic state 5 -1 on the lower work function bilayer NaCl/Ag(111) and Cu(111) surfaces (Supplementary Figs  ) 
In the main text, we focus on the characterization of 5 on bilayer NaCl/Au(111)  Characterization of charge bistable 5 is reported in Supplementary Figs    We first describe experiments on 5 on bilayer NaCl/Au(111), where 5 exhibits a geometry corresponding to the calculated 5OS geometry, and an open-shell electronic configuration 
We compare the experimental data on this species to calculations on 5OS with a triplet configuration, as theory predicts a triplet ground state for 5OS  For 5OS, the calculated frontier orbitals correspond to the SOMOs ψ1 and ψ2 (Fig  ), whose spin up levels are occupied and the spin down levels are empty 
Figure shows the DFT-calculated bond lengths of 5OS, where the two salient features, namely, the small difference in the bond lengths within each ring and the notably longer bond lengths in the pentagonal rings, agree with the open-shell resonance structure of 5 (Fig  )  Figure shows an AFM image of 5 adsorbed on bilayer NaCl/Au(111) that we assign as 5OS, where the bond-order differences qualitatively correspond to the calculated 5OS geometry (discussed and compared to the closed-shell state below) 
Differential conductance spectra (dI/dV(V), where I and V denote the tunneling current and bias voltage, respectively) acquired on assigned 5OS exhibit two peaks centered at -1 5 V and 1 6 V (Fig  ), which we assign to the positive and negative ion resonances (PIR and NIR), respectively  Figure shows the corresponding STM images acquired at the onset (V = -1 2
V/1 3 V) and the peak (V = -1 5 V/1 6 V) of the ionic resonances  To draw a correspondence between the STM images and the molecular orbital densities, we consider tunneling events as many-body electronic transitions between different charge states of 5OS (Fig  )  Within this framework, the PIR corresponds to transitions between 5 0 and the cationic state 5  
At the onset of the PIR at -1 2 V, an electron can only be detached from the SOMO ψ1 and the corresponding STM image at -1 2 V shows the orbital density of ψ1  Increasing the bias to the peak of the PIR at -1 5 V, it becomes possible to also empty the SOMO ψ2, such that the corresponding STM image shows the superposition of ψ1 and ψ2, that is, |ψ1| 2 + |ψ2| 2 (ref 
)  Similarly, the NIR corresponds to transitions between 5 0 and 5 -1   At the NIR onset of 1 3 V, only electron attachment to ψ2 is energetically possible  At 1 6 V, electron attachment to ψ1 also becomes possible, and the corresponding STM image shows the superposition of ψ1 and ψ2  The observation of the orbital densities of SOMOs, and not the hybridized HOMO and LUMO, proves the open-shell ground state of assigned 5OS 
Measurements of the monoradical species with a doublet ground state are shown in Supplementary Fig    Unexpectedly, another species of 5 was also experimentally observed that exhibited a closedshell ground state  In contrast to 5OS, where the frontier orbitals correspond to the SOMOs ψ1 and ψ2, DFT calculations predict orbitals of different shapes and symmetries for 5para and 5ortho, denoted as α and β and shown in Fig   
For 5ortho, α and β correspond to HOMO and LUMO, respectively  The orbitals are inverted in energy and occupation for 5para, where β is the HOMO and α is the LUMO  Fig  shows an AFM image of 5 that we assign as 5para  We experimentally infer its closed-shell state first by using qualitative bond order discrimination by AFM 
In high-resolution AFM imaging, chemical bonds with higher bond order are imaged brighter (that is, with higher frequency shift Δf) due to stronger repulsive forces, and they appear shorter   In Fig  , we label seven bonds whose bond orders show significant qualitative differences in the calculated 5ortho, 5para (Fig  ) and 5OS (Fig  ) geometries 
In 5para, the bonds b and d exhibit a higher bond order than a and c, respectively  This pattern is reversed for 5ortho, while the bond orders of the bonds a-d are all similar and small for 5OS  Furthermore, in 5para bond f exhibits a higher bond order than e, while in 5ortho and 5OS bonds e and f exhibit similar bond order (because they belong to Clar sextets) 
Finally, the bond labeled g shows a higher bond order in 5para than in 5ortho and 5OS  The AFM image of assigned 5para shown in Fig  indicates higher bond orders of the bonds b, d and f compared to a, c and e, respectively  In addition, the bond g appears almost point-like and with enhanced Δf contrast compared to its neighboring bonds, indicative of a high bond order (see Supplementary Fig  for height-dependent measurements) 
These observations concur with the calculated 5para geometry (Fig  )  Importantly, all these distinguishing bond-order differences are distinctly different in the AFM image of 5OS shown in Fig  , which is consistent with the calculated 5OS geometry (Fig  )  In the AFM images of 5OS (Fig  and Supplementary Fig  ), the bonds a-d at the pentagon apices appear with similar contrast and apparent bond length 
The bonds e and f at one of the terminal benzenoid rings also exhibit similar contrast and apparent bond length, while the central bond g appears longer compared to assigned 5para  Further compelling evidence for the closed-shell state of assigned 5para is obtained by STM and STS  dI/dV(V) spectra acquired on an assigned 5para species exhibit two peaks centered at -1 4 V (PIR) and 1 6 V (NIR) (Fig  ) 
STM images acquired at these biases (Fig  ) show the orbital densities of β (-1 4 V) and α (1 6 V)  First, the observation of α and β as the frontier orbitals of this species, and not the SOMOs, strongly indicates its closed-shell state  Second, consistent with AFM measurements that indicate good correspondence to the calculated 5para geometry, we observe β as the HOMO and α as the LUMO 
For 5ortho, α should be observed as the HOMO and β as the LUMO  We did not observe molecules with the signatures of 5ortho in our experiments  We observed molecules in open-(5OS, Fig  ) and closed-shell (5para, Fig  ) states in similar occurrence after their generation from 6 on the surface  We could also switch individual molecules between open-and closed-shell states as shown in Fig  and Supplementary Fig   
To this end, a change in the adsorption site of a molecule was induced by STM imaging at ionic resonances, which often resulted in movement of the molecule  The example presented in Fig  shows a molecule that was switched from 5para to 5OS and back to 5para  The switching is not directed, that is, we cannot choose which of the two species will be formed when changing the adsorption site, and we observed 5OS and 5para in approximately equal yields upon changing the adsorption site 
The molecule in Fig  is adsorbed on top of a defect that stabilizes its adsorption geometry on bilayer NaCl  At defect-free adsorption sites on bilayer NaCl, that is, without a third layer NaCl island or atomic defects in the vicinity of the molecule, 5 could be stably imaged neither by AFM nor by STM at ionic resonances (Supplementary Fig  ) 
Without changing the adsorption site, the state of 5 (open-or closedshell) never changed, including the experiments on bilayer NaCl/Ag(111) and Cu(111), on which the charge state of 5 could be switched (Supplementary Figs  )  Also on these lower work function surfaces, both open-and closed-shell species were observed for 5 0 and both showed charge bistability between 5 0 (5OS or 5para) and 5 -1 (Supplementary Figs  ) 
The geometrical structure of 5 -1 probed by AFM, and its electronic structure probed by STM imaging at the NIR (corresponding to transitions between 5 -1 and the dianionic state 5 -2 ), are identical within the measurement accuracy for the charged species of both 5OS and 5para  When cycling the charge state of 5 between 5 0 and 5 -1 several times, we always observed the same state (5OS or 5para) when returning to 5 0 , provided the molecule did not move during the charging/discharging process 
Based on our experimental observations we conclude that indeno[1,2-a]fluorene (5), the last unknown indenofluorene isomer, can be stabilized in and switched between an open-shell (5OS) and a closed-shell (5para) state on NaCl  For the former, both DFT and QD-NEVPT2 calculations predict a triplet electronic configuration 
Therefore, 5 can be considered to exhibit the spin-crossover effect, involving magnetic switching between high-spin (5OS) and low-spin (5para) states, coupled with a reversible structural transformation  So far, the spin-crossover effect has mainly only been observed in transition-metal-based coordination compounds with a near-octahedral geometry  
The observation that the switching between open-and closedshell states is related to changes in the adsorption site but is not achieved by charge-state cycling alone, indicates that the NaCl surface and local defects facilitate different electronic configurations of 5 depending on the adsorption site 
Gas-phase QD-NEVPT2 calculations predict that 5OS is the ground state, and the closed-shell 5para and 5ortho states are 0 11 and 0 21 eV higher in energy  The experiments, showing bidirectional switching between 5OS and 5para, indicate that a change in the adsorption site can induce sufficient change in the geometry of 5 (leading to a corresponding change in the ground state electronic configuration) and thus induce switching 
Switching between open-and closed-shell states in 5 does not require the breaking or formation of covalent bonds , but a change of adsorption site on NaCl where the molecule is physisorbed  Our results should have implications for single-molecule devices, capitalizing on the altered electronic and chemical properties of a system in π-diradical open-shell and closed-shell states such as frontier orbital and singlet-triplet gaps, and chemical reactivity 
For possible future applications as a single-molecule switch, it might be possible to also switch between open-and closed-shell states by changing the local electric field, such as by using chargeable adsorbates   Scanning probe microscopy measurements and sample preparation  STM and AFM measurements were performed in a home-built system operating at base pressures below 1×10 -10 mbar and a base temperature of 5 K  Bias voltages are provided with respect to the sample 
All STM, AFM and spectroscopy measurements were performed with carbon monoxide (CO) functionalized tips  AFM measurements were performed in non-contact mode with a qPlus sensor   The sensor was operated in frequency modulation mode with a constant oscillation amplitude of 0 5 Å  STM measurements were performed in constantcurrent mode, AFM measurements were performed in constant-height mode with V = 0 V, and I(V) and Δf(V) spectra were acquired in constant-height mode 
Positive (negative) values of the tip-height offset Δz represent tip approach (retraction) from the STM setpoint  All dI/dV(V) spectra are obtained by numerical differentiation of the corresponding I(V) spectra  STM and AFM images, and spectroscopy curves, were post-processed using Gaussian low-pass filters 
Au(111), Ag(111) and Cu(111) surfaces were cleaned by iterative cycles of sputtering with Ne + ions and annealing up to 800 K  NaCl was thermally evaporated on Au(111), Ag(111) and Cu(111) surfaces held at 323 K, 303 K and 283 K, respectively  This protocol results in the growth of predominantly bilayer (100)-terminated islands, with a minority of trilayer islands 
Sub-monolayer coverage of 6 on surfaces was obtained by flashing an oxidized silicon wafer containing the precursor molecules in front of the cold sample in the microscope  CO molecules for tip functionalization were dosed from the gas phase on the cold sample  Density functional theory calculations  DFT was employed using the PSI4 program package  
All molecules with different charge (neutral and anionic) and electronic (open-and closed-shell) states were independently investigated in the gas phase  The B3LYP exchangecorrelation functional with 6-31G basis set was employed for structural relaxation and singlepoint energy calculations  The convergence criteria were set to 10 −4 eV Å −1 for the total forces and 10 −6 eV for the total energies 
Multireference calculations  Multireference calculations were performed on the DFToptimized geometries using the QD-NEVPT2 level of theory , with three singlet roots and one triplet root included in the state-averaged calculation  A (10,10) active space (that is, 10 electrons in 10 orbitals) was used along with the def2-TZVP basis set  
Increasing either the active space size or expanding the basis set resulted in changes of about 50 meV for relative energies of the singlet and triplet states  These calculations were performed using the ORCA program package   Nucleus-independent chemical shift (NICS) calculations  Isotropic nucleus-independent chemical shift values were evaluated at the centre of each ring using the B3LYP exchangecorrelation functional with def2-TZVP basis set using the Gaussian 16 software package  
Starting materials (reagent grade) were purchased from TCI and Sigma-Aldrich and used without further purification  Reactions were carried out in flame-dried glassware and under an inert atmosphere of purified Ar using Schlenk techniques  Thin-layer chromatography (TLC) was performed on Silica Gel 60 F-254 plates (Merck) 
Column chromatography was performed on silica gel (40-60 µm)  Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker Varian Mercury 300 or Bruker Varian Inova 500 spectrometers  Mass spectrometry (MS) data were recorded in a Bruker Micro-TOF spectrometer  The synthesis of compound 6 was developed following the two-step synthetic route shown in Supplementary Fig  , which is based on the preparation of methylene-bridge polyarenes by means of Pd-catalyzed activation of benzylic C-H bonds  
Supplementary Figure | Synthetic route to obtain compound 6  The complex Pd2(dba)3 (20 mg, 0 02 mmol) was added over a deoxygenated mixture of 1,3-dibromo-2,4-dimethylbenzene (9, 100 mg, 0 38 mmol), boronic acid 10 (178 mg, 1 14 mmol), K2CO3 (314 mg, 2 28 mmol) and XPhos (35 mg, 0 08 mmol) in toluene (1:1, 10 mL), and the resulting mixture was heated at 90 °C for 2 h 
After cooling to room temperature, the solvents were evaporated under reduced pressure  The reaction crude was purified by column chromatography (SiO2; hexane:CH2Cl2 9:1) affording 11 (94 mg, 76%) as a colorless oil  The complex Pd(OAc)2 (7 mg, 0 03 mmol) was added over a deoxygenated mixture of terphenyl 11 (90 mg, 0 27 mmol), K2CO3 (114 mg, 0 83 mmol) and ligand L (26 mg, 0 06 mmol) in NMP (2 mL) 
The resulting mixture was heated at 160 °C for 4 h  After cooling to room temperature, H2O (30 mL) was added, and the mixture was extracted with EtOAc (3x15 mL)  The combined organic extracts were dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure  The reaction crude was purified by column chromatography (SiO2; hexane:CH2Cl2 9:1) affording compound 6 (8 mg, 11%) as a white solid  in AFM imaging due to their reduced adsorption height compared to the rest of the carbon atoms 
We attribute this observation to the significantly different lattice parameter of Cu(111) (2 57 Å) compared to Au(111) and Ag(111) (2 95 Å and 2 94 Å, respectively) , such that the apical carbon atoms of the pentagonal rings of 5 adsorb on the on-top atomic sites on Au(111) and Ag(111), but not on Cu(111) 
Our speculation is based on a previous study of polymers of 1 on Au(111) by Di Giovannantonio et al  , where both tilted and planar individual units of 1 were observed depending on whether the apical carbon atoms of the pentagonal rings in 1 adsorbed on the on-top or hollow sites of the surface, respectively 
Given the strong molecule-metal interaction, we found no electronic state signatures of 5 on all three metal surfaces  STM set point for AFM images: V = 0  e, Frontier orbital spectrum of 5 -1   In the anionic state, ψ2 becomes doubly occupied and ψ1 is the SOMO  Filled and empty circles denote occupied and empty orbitals, respectively 
For each panel, zero of the energy axis has been aligned to the respective highest-energy occupied orbital 
Context 2: '用户指南 * User Guide 02 CN 11 EN * 包装内含 使用前注意事项 快速引导 产品部件详情说明 操作说明 02 02 03 06 08 01 
•本产品支持在系统设置中进行瞳距调节 , 调节时请务必注意，最小瞳距可能会碰触鼻梁。当您佩戴头盔后，您 “显示”中进行手动调节，请注意设置使用不合适的瞳距，可能会引起视觉重影或者眼睛疲劳。 可在“设置” ► •本产品“护眼模式”经德国 TÜV Rheinland 低蓝光认证，通过软件算法降低三色通道中的蓝光量，来达到保护 “护眼” “色彩调节” 眼睛的作用，该模式下画面颜色偏黄，您可根据个人喜好在“设置” 中激活或关闭此功能。 ““显示” ► ► ► 包装内含： VR 头盔 / 手柄 × 2 / 1 5V AA 碱性干电池 × 4/ 眼镜支架 / 遮光鼻托 / 手柄挂绳 × 2 / USB-C 电源适配器 / USB-Cto C 2 0 数据线 / 快速指南 / 用户指南 / 安全与质保指南使用前注意事项 •本产品在开阔的室內环境使用体验最佳，建议至少预留 2×2 米 的空间。使用前请确认身体没有不适且周围环 境安全，特别是佩戴头盔在室内行走移动时，要尽量避免发生意外。 •不建议 12 岁及以下儿童使用本产品，建议将头盔、手柄和配件置于儿童够不到的位置，13 岁以上青少年须在 成人监护下使用，以免发生意外。 •本产品无近视调节功能，近视用户请佩戴眼镜使用并尽量避免近视眼镜被头盔的光学镜片磨伤或刮伤。建议在 使用和收纳时注意防护光学镜片，避免尖锐物体划伤镜片，擦拭清洁时请使用柔软的眼镜布，否则可能划伤镜片， 影响视觉效果。 •长时间使用可能引发轻微的昡晕或者眼疲劳，建议使用 30 分钟后适当休息，可通过眼保健操或观看远处物体缓 解眼疲劳。如果您的身体感到任何不适，请立即停止使用。如果不适持续，请咨询医生。 •当头盔镜片被阳光或紫外线照射时（尤其在户外、阳台、窗台及汽车内存放时），可能导致屏幕出现永久性黄斑。 请尽量避免该情况发生，此种屏幕损坏不在产品的质保范围内。 *本产品最终外观及功能以实物为准，部分地区包装内含物品有所差异，本说明仅供参考。 02 CN
六自由度 VR 体验 本产品可以追踪头盔和手柄前、后、左、右、上、下和旋转的运动状态，您在现实中的肢体运动会实时反映在虚 拟世界中。 由于没有任何线缆的束缚，您在虚拟世界自由探索时请确保游玩区域的安全。 1  建议准备一个整洁安全的体验空间：至少 2×2 米；保持房间明亮，避免在只有单色的墙或大面积玻璃、镜子类 反射物以及许多移动画面和物体的空间中使用。 2  撕下 VR 头盔前端摄像头上的保护膜，并佩戴手柄挂绳。 3  根据开机后的画面提示进行游玩区域的设定。 ❶ 安装电池 按箭头方向拔出电池盖侧边的绝缘纸 快速引导 提示：本产品虚拟的安全区提醒功能，不能完全保证您在设定好的游戏区域中的安全，请时刻注意周围的安全情况。 提示：建议使用 1 5V AA 碱性电池。 按照图示拨动电池盖拨钮打开电池盖更换电池。 03 CN
❷ 手柄开机 ❸ 头盔开机 ❹ 佩戴头盔，调节至清晰舒适的位置 首次开机：拔出绝缘纸，手柄自动开机（蓝灯闪烁） 非首次开机：短按手柄 Home 键开机（蓝灯闪烁） 长按头盔电源键 2 秒（蓝灯常亮） 调节旋钮转动绑带，使后脑垫套在头上，微调绑带长度及佩戴位置至视野清晰 04 提示：近视用户请佩戴眼镜或镜片插件使用，本产品不具备近视调节功能。 CN
❺ 微调顶绑带 微调顶绑带使其受力以减少额头压力 ❻ 瞳 距 调 节 在系统设置：“设置” ► “显示”界面中进行瞳距调节，点击“+”或“-”按钮可微调瞳距直至画面清晰 64mm 请勿 强行 掰动镜 筒，以 免造 成损坏 ！ 请注 意设 置使用 不合适 的瞳 距，可 能 会引起 视 觉重影 或 者眼睛 疲 劳。准 确 的瞳距 设 置有助 于 获得清 晰 的图像 并 减少眼睛 疲劳。 05 CN
产品部件详情说明 头盔状态指示灯 蓝灯常亮：开机进行中或工作状态 黄灯常亮：充电中，电量低于 98% 红灯常亮：充电中，电量低于 20% 绿灯常亮：充电完毕，电量大于 98% 或 充满 蓝灯闪烁：关机进行中 红灯闪烁：电量低于 20% 指示灯熄灭：休眠或关机 06 ① 电源键 开机：长按 2 秒 关机：长按 5 秒 复位：长按 10 秒 开机时，短按休眠 ② ③ ④ ⑤ 状态指示灯 贴脸泡棉 音量键 彩色透视摄像头 使用时请勿遮挡 ⑥ ⑦ ⑧ 顶部绑带 可拆卸 绑带旋钮 环境追踪摄像头 使用时请勿遮挡 ⑨ ⑩ ⑪ USB-C 接口 左 / 右喇叭 距离传感器 佩戴头盔后，系统自动唤醒 摘下头盔后，系统自动休眠 ⑫ ⑬ 眼球追踪摄像头 此功能仅 Pro 版支持 使用时请勿遮挡 面部追踪摄像头 此功能仅 Pro 版支持 使用时请勿遮挡 CN
手柄状态指示灯 熄灭：已连接或者关机 蓝灯常亮：固件升级模式 蓝灯闪烁：连接中 红蓝灯交替慢速闪烁：等待配对 ① ② 摇杆 菜单键 ③ Home 键 开机 : 短按关机 : 长按 6 秒退出应用 : 短按屏幕中心校正 : 长按 1 秒④ ⑤ ⑥ ⑦ 状态指示灯 抓握键 截屏键 扳机键 ⑧ ⑨ 电池盒 打开：拨动拨钮，电池盒弹出 安装：按压直至自动锁紧 追踪光环 使用时请勿遮挡 注：手柄挂绳可按图示将粗绳穿过细绳并锁紧在手柄尾端 07 CN
手柄硬件复位 如果手柄出现按 Home 键和任何按键均无反应或者头盔中虚拟手柄卡死不动的问题可拆装电池重新启动手柄。 近视用户配戴 本设备不具备近视调节功能，头盔可支持佩戴镜框宽度小于 150mm 的大多数标准眼镜。 操作说明 头控模式 未连接手柄的情况下，您可通过转动头部光标及点击头盔音量加减按键进行操作。 切换主控手柄射线 在主控菜单下，短按对应手柄的扳机键可以切换主控手柄的射线。 屏幕中心校正 戴着头盔直视前方，按住手柄 Home 键（或头控模式下头盔上的音量减键）1 秒以上，进行屏幕中心的校正将菜 单拉到当前视野朝向位置。 断开手柄 长按手柄 Home 键直至手柄状态指示灯红灯亮起并伴随振动产生时即可松手，此时手柄关机并断开与头盔的连接。 您无需刻意进行手柄关机操作，在以下状态下手柄会自动关机省电： •头盔进入深度休眠时（摘下头盔后一段时间） •头盔手柄管理界面解绑手柄时 •头盔关机时 添加新手柄 如需添加新手柄（头盔最多可同时连接一对手柄，即左右手柄各一只），或解绑手柄后再次连接 , 可进入“设置” “手 柄”，点击“配对”，同时按住手柄 Home 键和扳机键直至手柄状态指示灯红蓝交替闪烁时即可松开，然后根据 头盔画面提示操作。 ► 休眠 / 唤醒 方式一：摘下头盔一段时间后，系统自动休眠；戴上头盔时，系统自动唤醒。 方式二：短按头盔电源键也可以进行休眠或唤醒操作。 硬件复位 头盔硬件复位 如果头盔出现短按头盔电源键没有反应或头盔的画面卡死等问题，可以长按头盔电源键 10 秒以上重新启动头盔。 08 CN
安装眼镜支架 安装遮光鼻托 如您存在眼镜摩擦光学镜片或者压迫鼻梁的问题，请按照图示安装眼镜支架以增加间隔空间。 您可根据佩戴的舒适度选择是否安装。 如您感觉鼻子处漏光影响体验，请按照图示安装遮光鼻托配件。 由于眼睛空间密闭可能加剧起雾及出汗问题，您可根据喜好选择是否安装。 ❶ 摘下贴脸泡棉 ❷ 将眼镜支架按照图示安装在产品上 ❸ 将贴脸泡棉按照图示安装眼镜支架上 ❶ 摘下贴脸泡棉 ❸ 安装贴脸泡棉❷ 将遮光鼻托按照图示方式安装在贴脸泡棉上 注：按照图示拆卸眼镜支架 09 CN
更换贴脸泡棉 贴脸泡棉多次清洁和长时间使用后会变色和质地变软，您可酌情更换新泡棉。 更换顶绑带 摘下贴脸泡棉 ❸ 安装贴脸泡棉 按照图示捏住顶绑带金属扣，往下压到底然后抽出 ❷ •购买优质热门应用 •畅 聊 社 区， 与 众 多 PICO 玩 家 一起探索 VR 世界 •管理设备更便捷 •参与丰富互动活动 •更多精彩内容等你来发现 ❶ 微 信公 众 号：PICO VR抖音：PICO官 方 旗 舰 店哔 哩 哔 哩：PICO-VR官 方微 博：PICO-VR ❶ ❷ 10 CN
In The Box: VR Headset / 2 Controllers / 4 1 5V AA Alkaline Batteries / Glasses Spacer / Nose Pad / 2 Controller Lan- yards / USB-C Power Adapter / USB-C to C 2 0 Data Cable / Quick Guide / User Guide / Safety and WarrantyGuide Important Health & Safety Notes • This product is designed and intended to be used in an open and safe indoor area, free of anytripping or slipping hazards  To avoid accidents, remain conscious to the potential confines ofyour physical area and respect the boundary of your virtual area whenever you see it  Be sure towear the lanyards when using the Controllers  Make sure that there is enough space around yourhead and body (at least 2 meters by 2 meters) to stretch your arms to avoid damage or injury toyourself, others, and your surroundings  • This product is not recommended for children aged 12 and under  It is recommended to keep headsets,controllers and accessories out of the reach of children  Teenagers aged 13 and over must use it underadult supervision to avoid accidents  • This product is designed to accommodate most prescription glasses  Make sure to wear the VR Headsetin a manner in which the VR Headset lenses do not rub or impair your prescription lenses  • Prolonged use may cause dizziness or eye fatigue  It is recommended to take a break every 30 minutes Try relieving your eyestrain by looking at distant objects  If you feel any discomfort, stop using the prod- uct immediately  If the discomfort persists, seek medical advice • Do not expose the optical lenses to direct sunlight or other strong light sources  Exposure to directsunlight may cause permanent yellow spot damage on the screen  Screen damage caused by sunlightexposure or other strong sources of light is not covered by the warranty  • This product supports interpupillary distance (IPD) adjustment in system settings  When adjusting,please be aware that with the minimum IPD, it may touch the bridge of the nose  You can adjust the IPDaccording to your actual interpupillary distance in "Settings"►"Display"  Please note that using inap- propriate IPD may increase the risk of discomfort  • This product has an “Eye Protection Mode”, certified by TÜV Rheinland (Germany), which can protectyour eyes by reducing blue light in the three color channels using software algorithms  The screen ap- pears yellowish in this mode and you can turn this feature on/off in "Settings"►"Display"►"Color"►“- Eye Protection”  • Protect optical lenses during use and storage to prevent damage, such as scratches or exposure tostrong light or direct sunlight  * Product and packaging are updated regularly, and the functions and contents of the standalone headset may be upgraded in the future Therefore, the content, appearance and functionality listed in this manual and product packaging are subject to change and may notreflect the final product  These instructions are for reference only  * Carefully read this user guide before using the product and share this information with any other users, as it contains important safetyinformation  Keep the user guide as reference for the future  11 EN
6 Degrees of Freedom VR The device can track your translational and rotational movements in all directions (up/down, left/right,forward/backward, pitch, roll, and yaw)  Your movements in the real world will be captured and translatedto what you see in the virtual world when using the appropriate content  Ensure a safe environment before you start your VR experience  1  Clear a safe indoor area of at least 2 meters by 2 meters  Keep the room bright, avoid spaces with main- ly single-colored walls, glass, mirrors, moving pictures or other similar objects  2  Remove the protective film that covers the headset front cameras  Wear the lanyards connected to theControllers  3  Set up your environment by following instructions on the VR Headset screen  Install Batteries ❶Pull the tab to remove the insulating paper  Quick Guide 2 m 2m This product can not guarantee your safety with guardian system, you will need to always pay attention to the surrounding safety  * Note: 1 5V AA alkaline batteries should be used



ground_truth: Yes, individual molecules of indeno[1,2-a]fluorene can switch between open-shell and closed-shell states by changing their adsorption site on the surface.

prompt_front: Now, answer the following question based on the text below, only give me the answer and do not output any other words.

Question: What is the recommended space for using the VR headset?

Read the following text and answer briefly.

Context 2: Slide the toggle according to arrow direction toopen the battery case  12 EN
Power on the Controller ❷ First Start: The Controller will start automaticallyafter removing the insulating paper  Others: Short press the Home button for 1second until the status indicator flashes blue Power on the VR Headset ❸ Long press the Power button for 2 seconds untilthe status indicator turns blue Wear Your Headset for a Comfortable Fit and View ❹ Adjust the strap dial to turn the strap so that the back of your head rests on the padding  Fine-tune thelength and position of the strap to give a clear view  * Note: You can use this product with prescription glasses or lenses insert  13 EN
Fine-tune the Top Strap ❺ Fine-tune the head strap to reduce pressure on the forehead  Interpupillary Distance (IPD) Adjustment ❻ In System Setting, go to “Setting” ► “Display” to adjust IPD, tap “+” or “-” button to slightly adjust IPDuntil the picture is clear  14 64mm Please note that inappropriate IPD setting may cause ghosting or eyestrain Accurate IPD setting helps you get a clear imaging and ease eyestrain  EN
Product Details VR Headset Status Indicator Legend Blue: Powered on with battery over 20% Yellow: Charging: Battery is less than 98% Red: Charging: Battery is less than 20% Green: Charging: Battery is more than 98% or charge complete Blue flashing: Shutting down Red flashing: Battery is less than 20% Off: Sleeping or Powered off Power Power on: Long press for 2 seconds Power off: Long press for 5 seconds Hardware reset: Long press for 10 seconds Short press to enter sleep or wake up Status Indicator Face Cushion Volume ① ② ③ ④ ⑤ ⑥ ⑦ ⑧ RGB See Through Camera Do not block during use  Top Strap Removable Strap Dial Tracking Cameras Do not block during use  ⑨ ⑩ ⑪ USB-C Interface Left/Right Speaker Proximity Sensor The system wakes upwhen the VR headset isput on, sleeps when VRheadset is taken off  ⑫ ⑬ Eye Tracking Cameras Pro version only  Do not block during use  Face Tracking Camera Pro version only  Do not block during use  15 EN
Controller Status Indicator Legend Off: Connected or Powered off Blue: Firmware updating in progress Blue flashing: Searching for connection Red and blue flashing alternately: Pairing in progress 16 Joystick Menu ③ ① ② Home Power on: Short pressPower off: Long press for 6 secondsReturn home screen: Short pressScreen recentering: Press for 1 secondStatus Indicator Grip Capture Trigger ④ ⑤ ⑥ ⑦ ⑧ ⑨ Battery Case Open: Slide down the toggle andpop up the battery case  Lock: Push the battery case to lock  Tracking Ring Do not block during use  * Note: Pass the Controller Lanyardthrough the string as shown andlock at the end of the Controller EN
Operating Instructions Headset Control Mode If the Controller is not connected, you can interact with the home screen by moving your head to directthe crosshairs over your intended selection and clicking the Volume Up/Down button on the VR Headset  Switch the pointer of the master Controller In the home screen, short press the Trigger of the corresponding Controller to switch the pointer of themaster Controller  Screen re-centering Wear the VR Headset and look straight ahead, press and hold the Home button of the Controller or VRHeadset ( or the Volume Down button of the VR Headset in head control mode) for more than 1 second tore-center the screen  Disconnect the Controller Press and hold the Home button until the status indicator turns red and the Controller vibrates Controllers will automatically shut down to save power in the following cases:When the VR Headset enters deep sleep (a while after the VR Headset is taken off)When the Controller is unpairedWhen the VR Headset is powered off Add a new Controller If you need to add a new Controller (the VR Headset can only connect one left Controller and one rightController) or reconnect with an unpaired Controller  Go to “Settings” ► “Controller”, click on “Pair” Press and hold the Home button and the Trigger of the Controller at the same time until the red and bluelights of the Controller flashing alternately, and then follow the instructions on the VR Headset screen  Sleep / Wake up Option 1 (Proximity Sensor) Take off VR Headset for automatic sleeping: wear the VR Headset for automat- ic waking up  Option 2 (POWER Button) Press the Power button of the VR Headset for manual sleeping or waking up  Hardware reset VR Headset reset If the visual in the VR Headset freezes, or the VR Headset does not respond after short press the Powerbutton, you can press the Power button of the VR Headset for more than 10 seconds to reboot the VRHeadset  Controller reset If the virtual Controller, the Home button or any buttons of the Controller doesn\'t respond, remove andreinstall the battery case to restart the Controller  The VR Headset Adjustment This device has no myopia adjustment function  The VR Headset allows wearing most standard glasseswith a frame width of less than 150mm  to install Glasses Spacer to increase the space  You can install or not according to your situation  17 EN
Install Glasses Spacer Install Nose Pad If you have glasses collision with headset lens or pressure on the bridge of nose, please follow the pictureto install Glasses Spacer to increase the space  You can install or not according to your situation  If you feel light leaking from your nose, please follow the picture to install Nose Pad to block the light You can consider having it installed at your own discretion  Disassemble the Face Cushion  Install the Glasses Spacer on the Headset  ❸ ❶ ❷ Install the Face Cushion on the Glasses Spacer  Disassemble the Face Cushion  Install the Nose Pad on the Face Cushion  ❶ ❷ Install the Face Cushion on the Headset  ❸ * Note: Disassemble the Glasses Spacer 18 EN
Replace Face Cushion The Face Cushion will have the following phenomena such as color change, surface fluff, soft texture afterlong-term use and repeated cleaning  You can replace a new Face Cushion as needed  Replace Top Strap ❶ ❷ Disassemble the Face Cushion  Pinch the metal buckle of the top strap asshown, press it down and pull it out Install the Face Cushion on  ❸ ❷ ❶ • Purchase high-quality and trending apps • Join PICO Community and explore the VR worldwith other PICO players• Manage your device with ease • Engage in diverse and interactive activities • More exciting features waiting for you 19 EN
'
Context 3: Thalassaemia minor | definition of Thalassaemia minor by Medical dictionary
Thalassaemia minor | definition of Thalassaemia minor by Medical dictionary
https://medical-dictionary thefreedictionary com/Thalassaemia+minor
(redirected from Thalassaemia minor)
Related to Thalassaemia minor: thalassaemia major
Thalassemia describes a group of inherited disorders characterized by reduced or absent amounts of hemoglobin, the oxygen-carrying protein inside the red blood cells  There are two basic groups of thalassemia disorders: alpha thalassemia and beta thalassemia  These conditions cause varying degrees of anemia, which can range from insignificant to life threatening 
All types of thalassemias are considered quantitative diseases of hemoglobin, because the quantity of hemoglobin produced is reduced or absent  Usual adult hemoglobin is made up of three components: alpha globin, beta globin, and heme  Thalassemias are classified according to the globin that is affected, hence the names alpha and beta thalassemia  Although both classes of thalassemia affect the same protein, the alpha and beta thalassemias are distinct diseases that affect the body in different ways 
Beta thalassemia may be the most best-known type of thalassemia and is also called Cooley's anemia  It is caused by a change in the gene for the beta globin component of hemoglobin  Beta thalassemia causes variable anemia that can range from moderate to severe, depending in part on the exact genetic change underlying the disease  Beta thalassemia can be classified based on clinical symptoms  Beta thalassemia major usually causes severe anemia that can occur within months after birth  If left untreated, severe anemia can result in insufficient growth and development, as well as other common physical complications that can lead to a dramatically decreased life-expectancy  Fortunately, in developed countries beta thalassemia is usually identified by screening in the newborn period, before symptoms have developed  Children who are identified early can be started on ongoing blood transfusion therapy as needed  Although transfusion therapy prevents many of the complications of severe anemia, the body is unable to eliminate the excess iron contained in the transfused blood  Over time, the excess iron deposits in tissues and organs, resulting in damage and organ failure  Another medication must be administered to help the body eliminate the excess iron and prevent iron-over-load complications  Beta thalassemia intermedia describes the disease in individuals who have moderate anemia that only requires blood transfusions intermittently, if at all 
Alpha thalassemia is the result of changes in the genes for the alpha globin component of hemoglobin  There are two main types of alpha thalassemia disease: hemoglobin H disease and alpha thalassemia major  The two diseases are quite different from beta thalassemia as well as from one another  Individuals with hemoglobin H disease can experience events of hemolytic anemia—anemia caused by the rapid breakdown of the red blood cells  These events are thought to be triggered by various environmental causes, such as infection and/or exposure to certain chemicals  Hemoglobin H disease is in most cases milder than beta thalassemia  It does not generally require transfusion therapy  Alpha thalassemia major is a very serious disease that results in severe anemia that begins even before birth  Most affected babies do not survive to be born or die shortly after birth 
The thalassemias are among the most common genetic diseases worldwide  Both alpha and beta thalassemia have been described in individuals of almost every ancestry, but the conditions are more common among certain ethnic groups  Unaffected carriers of all types of thalassemia traits do not experience health problems  In fact, the thalassemia trait is protective against malaria, a disease caused by blood-borne parasites transmitted through mosquito bites  According to a widely accepted theory, most genetic changes—mutations—that cause thalassemia occurred multiple generations ago  Coincidentally, these mutations increased the likelihood that carriers would survive malaria infection  Survivors passed the mutation onto their offspring, and the trait became established throughout areas where malaria is common  As populations migrated, so did the thalassemia traits 
Beta thalassemia trait is seen most commonly in people with the following ancestry: Mediterranean (including North African, and particularly Italian and Greek), Middle Eastern, Indian, African, Chinese, and Southeast Asian (including Vietnamese, Laotian, Thai, Singaporean, Filipino, Cambodian, Malaysian, Burmese, and Indonesian)  Alpha-thalassemia trait is seen with increased frequency in the same ethnic groups  However, there are different types of alpha thalassemia traits within these populations  The frequency of hemoglobin H disease and alpha thalassemia major depends on the type of alpha thalassemia trait  The populations in which alpha thalassemia diseases are most common include Southeast Asians and Chinese (particularly Southern Chinese) 
It is difficult to obtain accurate prevalence figures for various types of thalassemia within different populations  This difficulty arises due to testing limitations in determining exact genetic diagnoses, as well as the fact that many studies have focused on small, biased hospital populations 
Two studies reflect prevalence figures that can be helpful counseling families and determining who to screen for beta thalassemia  Between the years of 1990 and 1996, the State of California screened more than 3 1 million infants born in the state for beta thalassemia  Approximately 1 in 114,000 infants had beta thalassemia major, with prevalence rates being highest among Asian Indians (about one in 4,000), Southeast Asians (about one in 10,000), and Middle Easterners (about one in 7,000)  Another type of beta thalassemia disease, E/beta thalassemia, was represented in approximately one in 110,000 births, all of which occurred in families of Southeast Asian ancestry  Among Southeast Asians, the prevalence of E/beta thalassemia was approximately one in 2,600 births  This is in keeping with the observation that hemoglobin E trait carrier rates are relatively high within the Southeast Asian population: 16% in a study of 768 immigrants to California, and up to 25% in some specific Southeast Asian populations such as Cambodians  While these California studies address some of the limitations of earlier population studies, the pattern observed in California is expected to be different in other areas of the United States and the world  For example, Italians are underrepresented in this population when compared to the population of the East Coast of the United States 
Determining prevalence figures for alpha thalassemia is even more difficult due to increased limitations in diagnostic testing  All types of alpha thalassemia disease are most common among people of Southeast Asian and Chinese descent, for reasons that become clearer with an understanding of the underlying genetics of alpha thalassemia  One study of 500 pregnant women in Northern Thailand estimated a frequency of one in 500 pregnancies affected by alpha thalassemia major, for example  Prevalence of alpha thalassemia disease is significantly lower in the United States primarily because of immigration patterns; although at least one state, California, has observed growing hemoglobin H disease incidence rates that are high enough to justify universal newborn screening for the condition 
Humans normally make several types of the oxygen-carrying protein hemoglobin  An individual's stage in development determines whether he or she makes primarily embryonic, fetal, or adult hemoglobins  All types of hemoglobin are made of three components: heme, alpha (or alpha-like) globin, and beta (or beta-like) globin  All types of thalassemia are caused by changes in either the alpha- or beta-globin gene  These changes cause little or no globin to be produced  The thalassemias are, therefore, considered quantitative hemoglobin diseases  All types of thalassemias are recessively inherited, meaning that a genetic change must be inherited from both the mother and the father  The severity of the disease is influenced by the exact thalassemia mutations inherited, as well as other genetic and environmental factors  There are rare exceptions, notably with beta thalassemia, where globin gene mutations exhibit a dominant pattern of inheritance in which only one gene needs to be altered in order to see disease expression  Scientists continue to study the causes  For instance, a new mutation for alpha-thalassemia was discovered for the first time among Iranian patients in 2004 
BETA-THALASSEMIA  Most individuals have two normal copies of the beta globin gene, which is located on chromosome 11 and makes the beta globin component of normal adult hemoglobin, hemoglobin A  There are approximately 100 genetic mutations that have been described that cause beta thalassemia, designated as either beta0 or beta + mutations  No beta globin is produced with a beta0 mutation, and only a small fraction of the normal amount of beta globin is produced with a beta + mutation 
When an individual has one normal beta globin gene and one with a beta thalassemia mutation, he or she is said to carry the beta thalassemia trait  Beta thalassemia trait, like other hemoglobin traits, is protective against malaria infection  Trait status is generally thought not to cause health problems, although some women with beta thalassemia trait may have an increased tendency toward anemia during pregnancy 
When two members of a couple carry the beta thalassemia trait, there is a 25% chance that each of their children will inherit beta thalassemia disease by inheriting two beta thalassemia mutations, one from each parent  The clinical severity of the beta thalassemia disease—whether an individual has beta thalassemia intermedia or beta thalassemia major—will depend largely on whether the mutations inherited are beta0 thalassemia or beta + thalassemia mutations  Two beta0 mutations generally lead to beta thalassemia major, and two beta+ thalassemia mutations generally lead to beta thalassemia intermedia  Inheritance of one beta0 and one beta + thalassemia mutation tends to be less predictable 
Although relatively uncommon, there are other thalassemia-like mutations that can affect the beta globin gene  Hemoglobin E is the result of a substitution of a single nucleotide  This change results in a structurally altered hemoglobin that is produced in decreased amounts  Therefore, hemoglobin E is unique in that it is both a quantitative (i e  thalassemia-like) and qualitative trait  When co-inherited with a beta thalassemia trait, it causes a disease that is almost indistinguishable from beta thalassemia disease  Large deletions around and including the beta globin gene can lead to delta/beta thalassemia or hereditary persistence of fetal hemoglobin (HPFH)  Interestingly, delta/beta thalassemia trait behaves very similarly to beta thalassemia trait in its clinical manifestations  However, HPFH trait does not tend to cause hemoglobin disease when co-inherited with a second thalassemia or other beta globin mutation 
ALPHA-THALASSEMIA  Most individuals have four normal copies of the alpha globin gene, two copies on each chromosome 16  These genes make the alpha globin component of normal adult hemoglobin, which is called hemoglobin A  Alpha globin is also a component of fetal hemoglobin and the other major adult hemoglobin called hemoglobin A2  Mutations of the alpha globin genes are usually deletions of the gene, resulting in absent production of alpha globin  Since there are four genes (instead of the usual two) to consider when looking at alpha globin gene inheritance, there are several alpha globin types that are possible 
Absence of one alpha globin gene leads to a condition known as silent alpha thalassemia trait  This condition causes no health problems and can be detected only by special genetic testing  Alpha thalassemia trait occurs when two alpha globin genes are missing  This can occur in two ways  The genes may be deleted from the same chromosome, causing the 'cis' type of alpha thalassemia trait  Alternately, they may be deleted from different chromosomes, causing the 'trans' type of alpha thalassemia trait  In both instances, there are no associated health problems, although the trait status may be detected by more routine blood screening 
Hemoglobin H disease results from the deletion of three alpha globin genes, such that there is only one functioning gene  Typically, this can occur when one parent carries the silent alpha thalassemia trait, and the other parent carries the 'cis' type of the alpha thalassemia trait  In this situation, there is a 25% chance for hemoglobin H disease in each of such a couple's children 
Hemoglobin H disease-like symptoms can also be a part of a unique condition called alpha thalassemia mental retardation syndrome  Alpha thalassemia mental retardation syndrome can be caused by a deletion of a significant amount of chromosome 16, affecting the alpha globin genes  This is usually not inherited, but rather occurs sporadically in the affected individual  Affected individuals have mild hemoglobin H disease, mild-to-moderate mental retardation, and characteristic facial features  This syndrome can also occur as a sex-linked form in which a mutation is inherited in a particular gene on the X-chromosome  This gene influences alpha globin production, as well as various other developmental processes  Individuals affected with this form of the syndrome tend to have more severe mental retardation, delayed development, nearly absent speech, characteristic facial features, and genital-urinary abnormalities  The remaining discussion will focus only on aspects of hemoglobin H disease 
Alpha thalassemia major results from the deletion of all four alpha globin genes, such that there are no functioning alpha globin genes  This can occur when both parents carry the 'cis' type of the alpha thalassemia trait  In this situation, there is a 25% chance for alpha thalassemia major in each of such a couple's children 
Beta thalassemia major is characterized by severe anemia that can begin months after birth  In the United States and other developed countries beta thalassemia is identified and treated early and effectively  Therefore, the following discussion of symptoms applies primarily to affected individuals in the past and unfortunately in some underdeveloped countries now  If untreated, beta thalassemia major can lead to severe lethargy, paleness, and delays in growth and development  The body attempts to compensate by producing more blood, which is made inside the bones in the marrow  However, this is ineffective without the needed genetic instructions to make enough functioning hemoglobin  Instead, obvious bone expansion and changes occur that cause characteristic facial and other changes in appearance, as well as increased risk of fractures  Severe anemia taxes other organs in the body—such as the heart, spleen, and liver—which must work harder than usual  This can lead to heart failure, as well as enlargement and other problems of the liver and spleen  When untreated, beta thalassemia major generally results in childhood death, usually due to heart failure  In 2004, the first known heart attack associated with beta thalassemia major was reported  Fortunately, in developed countries diagnosis is usually made early, often before symptoms have begun  This allows for treatment with blood transfusion therapy, which can prevent most of the complications of the severe anemia caused by beta thalassemia major  Individuals with beta thalassemia intermedia have a more moderate anemia that may only require treatment with transfusion intermittently, such as when infections occur and stress the body  As a person with beta thalassemia intermedia gets older, however, the need for blood transfusions may increase to the point that they are required on a regular basis  When this occurs their disease becomes more similar to beta thalassemia major  Other genetic and environmental factors can influence the course of the disease as well  For example, co-inheritance of one or two alpha thalassemia mutations can tend to ameliorate some of the symptoms of beta thalassemia disease, which result in part from an imbalance in the amount of alpha- and beta-globin present in the red blood cells 
Hemoglobin h disease
Absence of three alpha globin genes causes an imbalance of alpha and beta globin proteins in the red blood cells  The excess beta globin proteins tend to come together to form hemoglobin H, which is unable to release oxygen to the tissues  In addition, hemoglobin H tends to precipitate out in the cells, causing damage to the red blood cell membrane  When affected individuals are exposed to certain drugs and chemicals known to make the membrane more fragile, the cells are thought to become vulnerable to breakdown in large numbers, a complication called hemolytic anemia  Fever and infection are also considered to be triggers of hemolytic anemia in hemoglobin H disease  This can result in fatigue, paleness, and a yellow discoloration of the skin and whites of eyes called jaundice  Usually, the anemia is mild enough not to require treatment  Severe anemia events may require blood transfusion, however, and are usually accompanied by such other symptoms as dark feces or urine and abdominal or back pain  These events are uncommon in hemoglobin H disease, although they occur more frequently in a more serious type of hemoglobin H disease called hemoglobin H/Constant Spring disease  Individuals effected with this type of hemoglobin H disease are also more likely to have enlargement of and other problems with the spleen 
Alpha thalassemia major
Because alpha globin is a necessary component of all major hemoglobins and some minor hemoglobins, absence of all functioning alpha globin genes leads to serious medical consequences that begin even before birth  Affected fetuses develop severe anemia as early as the first trimester of pregnancy  The placenta, heart, liver, spleen, and adrenal glands may all become enlarged  Fluid can begin collecting throughout the body as early as the start of the second trimester, causing damage to developing tissues and organs  Growth retardation is also common  Affected fetuses usually miscarry or die shortly after birth  In addition, women carrying affected fetuses are at increased risk of developing complications of pregnancy and delivery  Up to 80% of such women develop toxemia, a disturbance of metabolism that can potentially lead to convulsions and coma  Other maternal complications include premature delivery and increased rates of delivery by cesarean section, as well as hemorrhage after delivery 
Thalassemia may be suspected if an individual shows signs that are suggestive of the disease  In all cases, however, laboratory diagnosis is essential to confirm the exact diagnosis and to allow for the provision of accurate genetic counseling about recurrence risks and testing options for parents and affected individuals  Screening is likewise recommended to determine trait status for individuals of high-risk ethnic groups 
The following tests are used to screen for thalassemia disease and/or trait:
hemoglobin electrophoresis with quantitative hemoglobin A2 and hemoglobin F
free erythrocyte-protoporphyrin (or ferritin or other studies of serum iron levels)
A complete blood count will identify low levels of hemoglobin, small red blood cells, and other red blood cell abnormalities that are characteristic of a thalassemia diagnosis  Since thalassemia trait can sometimes be difficult to distinguish from iron deficiency, tests to evaluate iron levels are important  A hemoglobin electrophoresis is a test that can help identify the types and quantities of hemoglobin made by an individual  This test uses an electric field applied across a slab of gel-like material  Hemoglobins migrate through this gel at various rates and to specific locations, depending on their size, shape, and electrical charge  Isoelectric focusing and high-performance liquid chromatography (HPLC) use similar principles to separate hemoglobins and can be used instead of or in various combinations with hemoglobin electrophoresis to determine the types and quantities of hemoglobin present  Hemoglobin electrophoresis results are usually within the normal range for all types of alpha thalassemia  However, hemoglobin A2 levels and sometimes hemoglobin F levels are elevated when beta thalassemia disease or trait is present  Hemoglobin electrophoresis can also detect structurally abnormal hemoglobins that may be co-inherited with a thalassemia trait to cause thalassemia disease (i e , hemoglobin E) or other types of hemoglobin disease (i e , sickle hemoglobin)  Sometimes DNA testing is needed in addition to the above screening tests  This can be performed to help confirm the diagnosis and establish the exact genetic type of thalassemia 
Diagnosis of thalassemia can occur under various circumstances and at various ages  Several states offer thalassemia screening as part of the usual battery of blood tests done for newborns  This allows for early identification and treatment  Thalassemia can be identified before birth through the use of prenatal diagnosis  Chorionic villus sampling (CVS) can be offered as early as 10 weeks of pregnancy and involves removing a sample of the placenta made by the baby and testing the cells  CVS carries a risk of causing a miscarriage that is between 0 5%-1%  Amniocentesis is generally offered between 15 and 22 weeks of pregnancy, but can sometimes be offered earlier  Two to three tablespoons of the fluid surrounding the baby is removed  This fluid contains fetal cells that can be tested  The risk of miscarriage associated with amniocentesis ranges from 0 33-0 5%  Pregnant woman and couples may choose prenatal testing in order to prepare for the birth of a baby that may have thalassemia  Alternately, knowing the diagnosis during pregnancy allows for the option of pregnancy termination  Preimplantation genetic diagnosis (PGD) is a relatively new technique that involves in-vitro fertilization followed by genetic testing of one cell from each developing embryo  Only the embryos unaffected by sickle cell disease are transferred back into the uterus  PGD is currently available on a research basis only and is relatively expensive 
Individuals with beta thalassemia major receive regular blood transfusions, usually on a monthly basis  This helps prevent severe anemia and allows for more normal growth and development  Transfusion therapy does have limitations, however  Individuals can develop reactions to certain proteins in the blood—called a transfusion reaction



ground_truth: It is recommended to have at least a 2x2 meter space for using the VR headset.

prompt_front: Now, answer the following question based on the text below, only give me the answer and do not output any other words.

Question: How are thalassemias classified?

Read the following text and answer briefly.

Context 3:  This can make locating appropriately matched donor blood more difficult  Although blood supplies in the United States are very safe, particularly relative to the past and to other areas of the world, there remains an increased risk of exposure to such blood-borne infections as hepatitis  Additionally, the body is not able to get rid of the excess iron that accompanies each transfusion  An additional medication called desferoxamine is administered, usually five nights per week over a period of several hours, using an automatic pump that can be used during sleep or taken anywhere the person goes  This medication is able to bind to the excess iron, which can then be eliminated through urine  If desferoxamine is not used regularly or is unavailable, iron overload can develop and cause tissue damage and organ damage and failure  The heart, liver, and endocrine organs are particularly vulnerable  Desferoxamine itself may rarely produce allergic or toxic side effects, including hearing damage  Signs of desferoxamine toxicity are screened for and generally develop in individuals who overuse the medication when body iron levels are sufficiently low  Overall, however, transfusion and desferoxamine therapy have increased the life expectancy of individuals with the most severe types of beta thalassemia major to the 4th or 5th decade  This can be expected to improve with time and increased developments in treatment, as well as for those with more mild forms of the disease 
New treatments offer additional options for some individuals with beta thalassemia major  There are various medications that target the production of red blood cells (i e  erythropoeitin) or fetal hemoglobin (i e  hydroxyurea and butyrate)  Their effectiveness in ameliorating the severity of beta thalassemia is currently being investigated  Another promising new treatment is bone marrow transplantation, in which the bone marrow of an affected individual is replaced with the bone marrow of an unaffected donor  If successful, this treatment can provide a cure  However, there is an approximately 10-15% chance the procedure could be unsuccessful (i e  the thalassemia returns); result in complications (i e  graft-versus-host disease); or result in death  The risk for specific individuals depends on current health status, age, and other factors  Because of the risks involved and the fact that beta thalassemia is a treatable condition, transplant physicians require a brother or sister donor who has an identically matched tissue type, called HLA type  HLA type refers to the unique set of proteins present on each individual's cells, which allows the immune system to recognize "self" from "foreign " HLA type is genetically determined, so there is a 25% chance for two siblings to be a match  Transplant physicians and researchers are also investigating ways to improve the safety and effectiveness of bone marrow transplantation  Using newborn sibling umbilical cord blood—the blood from the placenta that is otherwise discarded after birth but contains cells that can go on to make bone marrow—seems to provide a safer and perhaps more effective source of donor cells  Donors and recipients may not have to be perfect HLA matches for a successful transplant using cord blood cells  Trials are also underway to determine the effectiveness of "partial transplants," in which a safer transplant procedure is used to replace only a percentage of the affected individual's bone marrow  Other possible treatments on the horizon may include gene therapy techniques aimed at increasing the amount of normal hemoglobin the body is able to make 
Hemoglobin H disease is a relatively mild form of thalassemia that may go unrecognized  It is not generally considered a condition that will reduce one's life expectancy  Education is an important part of managing the health of an individual with hemoglobin H disease  It is important to be able to recognize the signs of severe anemia that require medical attention  It is also important to be aware of the medications, chemicals, and other exposures to avoid due to the theoretical risk they pose of causing a severe anemia event  When severe anemia occurs, it is treated with blood transfusion therapy  For individuals with hemoglobin H disease, this is rarely required  For those with the hemoglobin H/Constant Spring form of the disease, the need for transfusions may be intermittent or ongoing, perhaps on a monthly basis and requiring desferoxamine treatment  Individuals with this more severe form of the disease may also have an increased chance of requiring removal of an enlarged and/or overactive spleen 
Anemia — A blood condition in which the level of hemoglobin or the number of red blood cells falls below normal values  Common symptoms include paleness, fatigue, and shortness of breath 
Bilirubin — A yellow pigment that is the end result of hemoglobin breakdown  This pigment is metabolized in the liver and excreted from the body through the bile  Bloodstream levels are normally low; however, extensive red cell destruction leads to excessive bilirubin formation and jaundice 
Bone marrow — A spongy tissue located in the hollow centers of certain bones, such as the skull and hip bones  Bone marrow is the site of blood cell generation 
Bone marrow transplantation — A medical procedure used to treat some diseases that arise from defective blood cell formation in the bone marrow  Healthy bone marrow is extracted from a donor to replace the marrow in an ailing individual  Proteins on the surface of bone marrow cells must be identical or very closely matched between a donor and the recipient 
Desferoxamine — The primary drug used in iron chelation therapy  It aids in counteracting the life-threatening buildup of iron in the body associated with long-term blood transfusions 
Globin — One of the component protein molecules found in hemoglobin  Normal adult hemoglobin has a pair each of alpha-globin and beta-globin molecules 
Heme — The iron-containing molecule in hemoglobin that serves as the site for oxygen binding 
Hemoglobin — Protein-iron compound in the blood that carries oxygen to the cells and carries carbon dioxide away from the cells 
Hemoglobin A — Normal adult hemoglobin that contains a heme molecule, two alpha-globin molecules, and two beta-globin molecules 
Hemoglobin electrophoresis — A laboratory test that separates molecules based on their size, shape, or electrical charge 
Hepatomegaly — An abnormally large liver 
HLA type — Refers to the unique set of proteins called human leukocyte antigens  These proteins are present on each individual's cell and allow the immune system to recognize 'self' from 'foreign'  HLA type is particularly important in organ and tissue transplantation 
Hydroxyurea — A drug that has been shown to induce production of fetal hemoglobin  Fetal hemoglobin has a pair of gamma-globin molecules in place of the typical beta-globins of adult hemoglobin  Higher-than-normal levels of fetal hemoglobin can ameliorate some of the symptoms of thalassemia 
Iron overload — A side effect of frequent blood transfusions in which the body accumulates abnormally high levels of iron  Iron deposits can form in organs, particularly the heart, and cause life-threatening damage 
Jaundice — Yellowing of the skin or eyes due to excess of bilirubin in the blood 
Mutation — A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease, and can be transmitted to offspring 
Placenta — The organ responsible for oxygen and nutrition exchange between a pregnant mother and her developing baby 
Red blood cell — Hemoglobin-containing blood cells that transport oxygen from the lungs to tissues  In the tissues, the red blood cells exchange their oxygen for carbon dioxide, which is brought back to the lungs to be exhaled 
Screening — Process through which carriers of a trait may be identified within a population 
Splenomegaly — Enlargement of the spleen 
Because alpha thalassemia major is most often a condition that is fatal in the prenatal or newborn period, treatment has previously been focused on identifying affected pregnancies in order to provide appropriate management to reduce potential maternal complications  Pregnancy termination provides one form of management  Increased prenatal surveillance and early treatment of maternal complications is an approach that is appropriate for mothers who wish to continue their pregnancy with the knowledge that the baby will most likely not survive  In recent years, there have been a handful of infants with this condition who have survived long-term  Most of these infants received experimental treatment including transfusions before birth, early delivery, and even bone marrow transplantation before birth, although the latter procedure has not yet been successful  For those infants that survive to delivery, there seems to be an increased risk of developmental problems and physical effects, particularly heart and genital malformations  Otherwise, their medical outlook is similar to a child with beta thalassemia major, with the important exception that ongoing, life-long blood transfusions begin right at birth 
As discussed above, the prognosis for individuals with the most serious types of thalassemia has improved drastically in the last several years following recent medical advances in transfusion, chemo-, and transplantation therapy  Advances continue and promise to improve the life expectancy and quality of life further for affected individuals 
"First Known Heart Attack Associated With Beta-thalassemia Major Reported " Heart Disease Weekly February 22, 2004: 10 
"Novel Alpha-thalassemia Mutations Identified " Hematology Week January 26, 2004: 19 
Children's Blood Foundation  333 East 38th St , Room 830, New York, NY 10016-2745  (212) 297-4336  cfg@nyh med cornell edu 
Cooley's Anemia Foundation, Inc  129-09 26th Ave  #203, Flushing, NY 11354  (800) 522-7222 or (718) 321-2873  http://www thalassemia org 
March of Dimes Birth Defects Foundation  1275 Mamaroneck Ave , White Plains, NY 10605  (888) 663-4637  resourcecenter@modimes org  http://www modimes org 
National Heart, Lung, and Blood Institute  PO Box 30105, Bethseda, MD 20824-0105  (301) 592-8573  nhlbiinfo@rover nhlbi nih gov  http://www nhlbi nih gov 
National Organization for Rare Disorders (NORD)  PO Box 8923, New Fairfield, CT 06812-8923  (203) 746-6518 or (800) 999-6673  Fax: (203) 746-6481  http://www rarediseases org 
Bojanowski J  "Alpha Thalassemia Major: The Possibility of Long-Term Survival " Pamphlet from the Northern California Comprehensive Thalassemia Center  (1999) 
Children's Hospital Oakland, Northern California Comprehensive Thalassemia Center website  http://www thalassemia com 
Cooley's Anemia Foundation, Inc  website  http://www thalassemia org/gohome html 
Joint Center for Sickle Cell and Thalassemic Disorders website  http://cancer mgh harvard edu/medOnc/sickle htm 
[thal″ah-se´me-ah]
a heterogeneous group of hereditary hemolytic anemias marked by a decreased rate of synthesis of one or more hemoglobin polypeptide chains, classified according to the chain involved (α, β, δ); the two major categories are α- and β-thalassemia 
α-thalassemia (alpha-thalassemia) that caused by diminished synthesis of alpha chains of hemoglobin  The homozygous form is incompatible with life, the stillborn infant displaying severe hydrops fetalis  The heterozygous form may be asymptomatic or marked by mild anemia 
β-thalassemia (beta-thalassemia) that caused by diminished synthesis of beta chains of hemoglobin  The homozygous form is called t  major and the heterozygous form is called t  minor 
thalassemia ma´jor the homozygous form of β-thalassemia, in which hemoglobin A is completely absent; it appears in the newborn period and is marked by hemolytic, hypochromic, microcytic anemia; hepatosplenomegaly; skeletal deformation; mongoloid facies; and cardiac enlargement 
thalassemia mi´nor the heterozygous form of β-thalassemia; it is usually asymptomatic, but there may be mild anemia 
sickle cell–thalassemia a hereditary anemia involving simultaneous heterozygosity for hemoglobin S and thalassemia 
thal·as·se·mi·a
, thalassanemia (thal'ă-sē'mē-ă, thă-las-ă-nē'mē-ă),
Any of a group of inherited disorders of hemoglobin metabolism in which there is impaired synthesis of one or more of the polypeptide chains of globin; several genetic types exist, and the corresponding clinical picture may vary from barely detectable hematologic abnormality to severe and fatal anemia 
[G  thalassa, the sea, + haima, blood]
/thal·as·se·mia/ (thal″ah-se´me-ah) a heterogeneous group of hereditary hemolytic anemias marked by a decreased rate of synthesis of one or more hemoglobin polypeptide chains, classified according to the chain involved (α, β, δ); the two major categories are α- and β-thalassemia 
α-thalassemia that caused by diminished synthesis of alpha chains of hemoglobin  The homozygous form is incompatible with life, the stillborn infant displaying severe hydrops fetalis  The heterozygous form may be asymptomatic or marked by mild anemia 
β-thalassemia that caused by diminished synthesis of beta chains of hemoglobin  The homozygous form is called t  major and the heterozygous form is called t  minor 
thalassemia ma´jor the homozygous form of &#x03B2;, in which hemoglobin A is completely absent; it appears in the newborn period and is marked by hemolytic, hypochromic, microcytic anemia, hepatosplenomegaly, skeletal deformation, mongoloid facies, and cardiac enlargement 
thalassemia mi´nor the heterozygous form of &#x03B2;, usually asymptomatic, although there is sometimes mild anemia 
(thăl′ə-sē′mē-ə)
An inherited form of anemia occurring chiefly among people of Mediterranean descent, caused by faulty synthesis of part of the hemoglobin molecule  Also called Mediterranean anemia 
thal′as·se′mic adj 
[thal′əsē′mē·ə]
Etymology: Gk, thalassa, sea, a + haima, without blood
production and hemolytic anemia characterized by microcytic, hypochromic red blood cells  Thalassemia is caused by inherited deficiency of alpha- or beta-globin synthesis  See also hemochromatosis, hemosiderosis 
Beta thalassemia, clinical thalassemia, Cooley's anemia, Mediterranean anemia, thalassemia major Hematology A group of genetic diseases by underproduction of hemoglobin due to mutations in the beta globin gene, which is more common in Mediterraneans Heredity Parents are carriers–heterozygotes; one in 4 children is homozygous for the mutation and thus has full-blown disease Clinical See Anemia  Cf Sickle cell anemia 
α-thalassemia
Hemoglobin Barts Hematology An inherited condition caused by a defect in the synthesis of the Hb α chain; Hb Barts hemoglobinopathy is characterized by the presence of 4 gamma chains; it is more common in southeast Asians; the most severe form of alpha thalassemia causes stillbirth due to hydrops fetalis Heredity Parents are carriers–heterozygotes; one in 4 children is homozygous for the mutation and thus has full-blown disease Clinical Pallor, fatiguability, FTT, fever, infections, diarrhea Management Transfusions
Thalassemia major Hematology A hemoglobinopathy caused by a defect in the synthesis of Hb β chain Clinical Pallor, fatigability, FTT, fever due to infections, diarrhea, bone deformities, hepatosplenomegaly Management Transfusions, but iron overload can damage the heart, liver, and endocrine systems, ergo iron chelation–early use of deferiprone, deferoxamine ↓ transfusion-related iron overload and may protect against DM, cardiac disease, early death
δ-thalassemia
Hematology A condition characterized by a defect of Hb A2–α2δ2; because Hb A2 comprises only 3% of the circulating Hb, even its complete absence; δ-thalassemia has little clinical or hematologic impact
γ-thalassemia
Hematology A condition characterized by a defect of gamma–γ Hb chains found in Hb F–α2γ2; because Hb F is present primarily in the fetus and newborns, it is rarely seen outside of the neonatal period, but may cause transient neonatal hemolytic anemia 
, thalassanemia (thal'ă-sē'mē-ă, -ă-să-nē'mē-ă)
Any of a group of inherited disorders of hemoglobin metabolism in which there is impaired synthesis of one or more of the polypeptide chains of globin; several genetic types exist, and the corresponding clinical picture may vary from barely detectable hematologic abnormality to severe and fatal anemia  People of Mediterranean, extraction are more often affected than others by this type of anemia 
Synonym(s): thalassaemia, thalassanaemia 
Any of a group of inherited disorders of hemoglobin metabolism with impaired synthesis of one or more polypeptide chains of globin; several genetic types exist 
<a href="https://medical-dictionary thefreedictionary com/Thalassaemia+minor">thalassemia</a>
Barts hemoglobin
beta hemoglobinopathy
beta-delta thalassemia
beta-thalassaemia
Bite Cell
black gallstone
I know of a couple, totally unrelated and unbeknownst to them, who are silent carriers of Thalassaemia minor 
Pakistan: Genetic factor: All in the genes
But, unfortunately, when one person with thalassaemia minor carrier happens to marry another with the same diagnosis, there is a strong possibility that their child would be thalassaemia major, as happened in the case of Taneja 
' My life depends upon a monthly blood transfusion '
0] thalassaemia demonstrates variable severity, ranging from a condition similar to [beta] thalassaemia minor to something approaching thalassaemia major 
A retrospective review of homozygous haemoglobin E patients
Thal, Alan P 
thalame
thalamencephalic
thalamencephalon
thalamic
thalamic fasciculus
thalamic nucleus
thalamic pain syndrome
thalamic peduncle
thalamic radiation
thalamo-
thalamocoele
thalamocortical
thalamocortical fibers
thalamogeniculate artery
thalamolenticular
thalamoperforating artery
thalamostriate radiation
thalamotuberal artery
Thalassaemia minor
thalassaemiaor Cooley's disease
thalassemic facies
thalasso-
Thalassobacter
Thalassobacter utilis
thalassoplankton
thalassoposia
thalidomide neuropathy
Thalidomider
thallium poisoning
Thalarctos
THALAS
Thalasaemia
Thalassaemia Association of Malaysia
thalassaemia major
Thalassaemias
thalassaemic
thalassanaemia
Thalassemia Action Group
Thalassemia Clinical Research Network
thalassemia syndrome



ground_truth: According to the globin that is affected (alpha or beta).