bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyrrole Hemithioindigo Antimitotics with Near‐Quantitative Bidirectional Photoswitching that Photocontrol Cellular Microtubule Dynamics with Single‐Cell Precision**
Authors: Sailer Alexander , Meiring Joyce C. M. , Heise Constanze , Pettersson Linda N. , Akhmanova Anna , Thorn‐Seshold Julia , Thorn‐Seshold Oliver
Published: August 2021

We report the first cellular application of the emerging near‐quantitative photoswitch pyrrole hemithioindigo, by rationally designing photopharmaceutical PHTub inhibitors of the cytoskeletal protein tubulin. PHTubs allow simultaneous visible‐light imaging and photoswitching in live cells, delivering cell‐precise photomodulation of microtubule dynamics, and photocontrol over cell cycle progression and cell death. This is the first acute use of a hemithioindigo photopharmaceutical for high‐spatiotemporal‐resolution biological control in live cells. It additionally demonstrates the utility of near‐quantitative photoswitches, by enabling a dark‐active design to overcome residual background activity during cellular photopatterning. This work opens up new horizons for high‐precision microtubule research using PHTubs and shows the cellular applicability of pyrrole hemithioindigo as a valuable scaffold for photocontrol of a range of other biological targets.
Ru‐NHC‐katalysierte asymmetrische Hydrierung von 2‐Chinolonen zu chiralen 3,4‐Dihydro‐2‐chinolonen
Authors: Hu Tianjiao , Lückemeier Lukas , Daniliuc Constantin , Glorius Frank
Published: August 2021

Die enantioselektive Hydrierung ungesättigter Verbindungen zur Erzeugung chiraler dreidimensionaler Motive ist eine der einfachsten und wichtigsten Transformationen in der synthetischen Chemie. Wir haben die RuII‐NHC‐katalysierte asymmetrische Hydrierung von 2‐Chinolonen unter milden Reaktionsbedingungen realisiert. Alkyl‐, aryl‐ und halogensubstituierte optisch aktive Dihydro‐2‐chinolone wurden in hoher Ausbeute mit mäßigen bis exzellenten Enantioselektivitäten erhalten. Die Reaktion bietet einen effizienten und atomökonomischen Weg zur Synthese von einfachen chiralen 3,4‐Dihydro‐2‐chinolonen. Die erhaltenen Produkte können weiter zu Tetrahydrochinolinen und Octahydrochinolonen reduziert werden.
Realizing Record‐High Electroluminescence Efficiency of 31.5 % for Red Thermally Activated Delayed Fluorescence Molecules
Authors: Cai Zheyi , Wu Xing , Liu Hao , Guo Jingjing , Yang Dezhi , Ma Dongge , Zhao Zujin , Tang Ben Zhong
Published: August 2021

Tailor‐made red thermally activated delayed fluorescence (TADF) molecules comprised of an electron‐withdrawing pyrazino[2,3‐f][1,10]phenanthroline‐2,3‐dicarbonitrile core and various electron‐donating triarylamines are developed. They can form intramolecular hydrogen‐bonding, which is conducive to improving emission efficiency and promoting horizontal orientation and show near infrared (NIR) emissions (692–710 nm) in neat films and red delayed fluorescence (606–630 nm) with high photoluminescence quantum yields (73–90%) in doped films. They prefer horizontal orientation with large horizontal dipole ratios in films, rendering high optical out‐coupling factors (0.39–0.41). Their non‐doped OLEDs exhibit NIR lights (716–748 nm) with maximum external quantum efficiencies (ηext,max) of 1.0–1.9%. And their doped OLEDs radiate red lights (606–648 nm) and achieve record‐beating ηext,max of up to 31.5%. These new red TADF materials should have great potentials in display and lighting devices.
A Biocatalytic Cascade in an Ultrastable Mesoporous Hydrogen‐Bonded Organic Framework for Point‐of‐Care Biosensing
Authors: Tang Zhuopeng , Li Xinyi , Tong Linjing , Yang Huangsheng , Wu Jiayi , Zhang Xiliu , Song Ting , Huang Siming , Zhu Fang , Chen Guosheng , Ouyang Gangfeng
Published: August 2021

Herein, we report the first example of using mesoporous hydrogen‐bonded organic frameworks (MHOFs) as the protecting scaffold to organize a biocatalytic cascade. The confined microenvironment of MHOFs has robust and large transport channels, allowing the efficient transport of a wide range of biocatalytic substrates. This new MHOF‐confined cascade system shows superior activity, extended scope of catalytic substrates, and ultrahigh stability that enables the operation of complex chemical transformations in a porous carrier. In addition, the advantages of MHOF‐confined cascades system for point‐of‐care biosensing are also demonstrated. This study highlights the advantages of HOFs as scaffold for multiple enzyme assemblies, which has huge potential for mimicking complex cellular transformation networks in a controllable manner.
Synthesis of D‐π‐A‐π‐D photoinitiator with high‐photoinitiation efficiency by restricting photoinduced isomerization process
Authors: Lu Hongwei , Zhu Xiaoqun
Published: August 2021

In this work, we designed a new D‐π‐A‐π‐D LED photoinitiator BBFC with high molar excitation coefficient and photoinitiation efficiency based on the principle of inhibition of photoisomerization. Via introduction of benzene ring on the BFC, which we have reported before, the absorption wavelength, molar excitation coefficient and photoinitiation efficiency of BBFC were greatly improved. The characterization and theoretical calculation proved BBFC has no photoisomerization, for the change of the configuration of BBFC requiring high energy due to the steric effect. BBFC has higher initiation efficiency than that of commercial photoinitiator ITX with little content under air condition. This might have potential to design new D‐π‐A‐π‐D molecules with high‐photoinitiation efficiency and contribute the field of photo polymerization.
Amazon‐sustainable‐flour from açaí seeds added to starch films to develop biopolymers for active food packaging
Authors: Romani Viviane P. , Martins Vilásia G. , da Silva Ayla S. , Martins Paola C. , Nogueira Daiane , Carbonera Nádia
Published: August 2021

The wide consumption of açaí fruit results in large amounts of seeds which end up in waste. These seeds have an advantageous composition for the development of biopolymers due to their fibers content and active components (responsible by functional properties as antioxidant capacity). In the present work, active polymers were generated incorporating açaí seed flour in sustainable films produced using starch from broken rice grains as matrix. The effects of different seed flour content (0%, 5%, 10%, and 15%) were studied on the physicochemical and structural properties of the polymers, and their antioxidant capacity. The packaging‐related properties were affected by the açaí seed flour incorporation mainly due to its high‐fiber content and polyphenolic compounds. The physicochemical and structural properties results demonstrated that the incorporation of 5% of açaí seed flour was the most appropriate, because of its better distribution in the film matrix. Free radical scavenging and reducing power assays indicated the antioxidant potential of the açaí seed flour incorporated films. Thus, active and sustainable polymers for food packaging can be obtained from açaí seeds and broken rice grains, generating new polymers and converting them into valuable raw materials in the market.
Mechanobiological conceptual framework for assessing stem cell bioprocess effectiveness
Authors: Kim Mee‐Hae , Kino‐oka Masahiro
Published: August 2021

Fully realizing the enormous potential of stem cells requires developing efficient bioprocesses and optimizations founded in mechanobiological considerations. Here, we emphasize the importance of mechanotransduction as one of the governing principles of stem cell bioprocesses, underscoring the need to further explore the behavioral mechanisms involved in sensing mechanical cues and coordinating transcriptional responses. We identify the sources of intrinsic, extrinsic, and external noise in bioprocesses requiring further study, and discuss the criteria and indicators that may be used to assess and predict cell‐to‐cell variability resulting from environmental fluctuations. Specifically, we propose a conceptual framework to explain the impact of mechanical forces within the cellular environment, identify key cell state determinants in bioprocesses, and discuss downstream implementation challenges.
Evaluation of single‐use tangential flow filtration technology for purification of activated polysaccharides used in conjugate vaccine manufacturing
Authors: Motevalian Seyed Pouria , Steen Jonathan , De Leon Janine , Sriskanda Verl , Carino Ivette , Prashad Amar S. , Carrillo Conde Brenda , Arve Bo
Published: August 2021

Over the past decade, single‐use tangential flow filtration (TFF) technologies have emerged to reduce system preparation time, promote fast and flexible product change over, and ultimately shorten process development and manufacturing time/cost. In this study, the performance of a recently developed Pellicon® single‐use TFF capsule was compared against traditional Pellicon® cassettes by assessing TFF process performance (such as flux, residuals clearance, and yield) and post‐purification product attributes (such as concentration and mass‐weighted average molecular weight). Good scaling was shown by comparing process performance and product attributes across different scales and formats. Additionally, similar TFF process performance and post‐purification product attributes were observed for the single‐use capsule compared to the reusable TFF cassettes. The capsule requires a smaller flush than the cassette, and it is easier to use since it does not require a compression holder or pre‐sanitization. The results provide insight into the application of the single‐use TFF capsule and scalability of TFF processes for the purification of conjugate vaccines.
Four New Triterpenoid Saponins from the Root of Ilex centrochinensis
Authors: Yang Hang , Lu Yan‐Xia , Shi Yu , Deng Xue‐Ying , Yi Ying‐Tao , Li Lu‐Jun , Hu Ze‐Hua
Published: August 2021

One new siaresinolic acid saponin (1) and three new rotundic acid saponins (2–4) were isolated from the roots of Ilex centrochinensis. Their structures were confirmed by detailed analysis of standard spectroscopic data (IR, MS, 1D and 2D NMR). Compounds 1–4 exhibited anti‐inflammatory activity by inhibiting nitric oxide production in a lipopolysaccharide‐induced RAW264.7 cell inflammatory model. However, they showed no significant lipid‐lowering activity against the production of triglycerides in the lipid‐accumulation model of HepG2 cells induced by oleic acid.
Recent Progresses in Carbon Counter Electrode Materials for Perovskite Solar Cells and Modules
Authors: Xu Chang , Zhao Xuan , Ma Jingyuan , Guo Jiajing , Ma Tingli , Wu Mingxing
Published: August 2021

Though perovskite solar cells (PSCs) or modules (PSMs) are being developed at an unprecedented speed, several obstacles remain to their commercialization. One of the difficult problems is the expensive and unstable Au and Ag counter electrode. Therefore, highly effective, stable, and low‐cost counter electrode materials should be explored. Among various counter electrode materials, carbon is one of the most promising substitutes for their rich sources, low cost, outstanding electrochemical performance, and diversified surface functions. This review summarizes recent achievements of carbon counter electrode materials, which included commercial carbon paste, carbon black, graphite, graphene, carbon nanotubes and their synthetic approaches, modifications, and structure‐function relationships. Moreover, large‐scale carbon counter electrode in PSCs or PSMs are specifically discussed. Hopefully, this recapitulative analysis will draw the attention of relevant researchers to re‐understand the importance of counter electrode and clarify what should be noticed to develop qualified counter electrode materials for PSCs or PSMs.
Porphyrins and Polyoxometalate Scaffolds
Authors: Lamare Raphaël , Ruppert Romain , Boudon Corinne , Ruhlmann Laurent , Weiss Jean
Published: August 2021

Polyoxometalates (POMs) can act as unique reservoirs for multiple electron transfers. As POMs display only weak absorption in the visible spectrum, they can be associated with chromophores such as porphyrins and porphyrin antennae. In this Minireview, the research dedicated to the combination of porphyrins and polyoxometalates is put in context and the state of the art identifying the challenges addressed in the optimization of hybrid materials for applications is detailed.
Polycationic Redox‐Active Cyclophanes with Integrated Electron‐Rich Diboron Units
Authors: Filbeck Erik , Widera Anna , Kaifer Elisabeth , Himmel Hans‐Jörg
Published: August 2021

Cationic cyclophanes are widely used in a variety of applications in supramolecular chemistry and materials science. In this work the authors systematically study the integration of electron‐rich diboron units with BII atoms into polycationic cyclophanes with viologen‐like electron‐acceptor units. They also report a first hexacationic cage‐compound in which three diboron units connect two tris(4‐pyridyl)triazine acceptor units. Moreover, di‐ and tetracationic open‐structure compounds, in which one diboron unit connects two bispyridyl groups, were synthesized and the properties compared to those of the corresponding closed structures (cyclophanes). The combination of diboron electron‐donor units and bi‐ or oligopyridyl electron‐acceptor units leads to intriguing optical and redox properties.
Palliative care and coping in patients with acute myeloid leukemia: Mediation analysis of data from a randomized clinical trial
Authors: Nelson Ashley M. , Amonoo Hermioni L. , Kavanaugh Alison R. , Webb Jason A. , Jackson Vicki A. , Rice Julia , Lavoie Mitchell W. , Fathi Amir T. , Brunner Andrew M. , Greer Joseph A. , Temel Jennifer S. , El‐Jawahri Areej , LeBlanc Thomas W.
Published: August 2021

Background

It has been shown previously that integrated palliative care for patients with acute myeloid leukemia (AML) during intensive chemotherapy leads to improvements in quality of life (QOL) and mood. Coping has been shown to mediate palliative care interventions in advanced cancer; the mechanisms by which improvements occur among patients with AML remain unexplained.

Methods

The authors conducted a secondary analysis of data from a multisite randomized trial of integrated palliative and oncology care (IPC; n = 86) versus usual care (n = 74) for hospitalized patients with AML undergoing intensive chemotherapy. IPC patients met with palliative care at least twice weekly during their initial and subsequent hospitalizations. Patients completed the Functional Assessment of Cancer Therapy–Leukemia, the Hospital Anxiety and Depression Scale, and the Brief Coping Orientation to Problems Experienced Inventory to assess QOL, mood, and coping at the baseline and at weeks 2, 4, 12, and 24. Linear regression models were used to assess the effect of IPC on coping. Causal mediation regression models were used to examine whether changes in coping mediated intervention effects on patient‐reported outcomes at week 2.

Results

One hundred sixty eligible patients (68.1%) were enrolled. Those randomized to IPC reported improvements in approach‐oriented coping (P < .01) and reductions in avoidant coping (P < .05). These changes in coping mediated the intervention effects on QOL (95% CI, 2.14‐13.63), depression (95% CI, –2.05 to –0.27), and anxiety symptoms (95% CI, –1.25 to –0.04). Changes in approach‐oriented and avoidant coping accounted for 78% of the total palliative care intervention effect on QOL, for 66% of the effect on depression, and for 35% of the effect on anxiety symptoms.

Conclusions

Palliative care integrated during intensive chemotherapy for patients with AML facilitates coping strategy use. Improvement in coping skills accounts for a substantial proportion of the effect from a palliative care intervention on patient‐reported outcomes.
Energy‐aware disaster backup among cloud datacenters using multiobjective reinforcement learning in software defined network
Authors: Yi Shanwen , Li Xiaole , Wang Hua , Qin Yao , Yan Jiaxin
Published: August 2021

The transmission process of disaster backup with long distance and massive data causes huge energy consumption. Reducing the number of occupied intermediate forwarding devices and shortening the transmission completion time are two key factors for energy saving. Not jointly considering them, previous work can hardly realize optimal energy‐aware transmission only by single objective optimization. For the first time, we leverage multiobjective reinforcement learning to simultaneously minimize the number of occupied intermediate forwarding devices and the transmission completion time in software defined network. We propose two‐level reinforcement learning, consisting of search and selection operation. In the internal reinforcement learning, we aim to reduce hop number, improve node sharing degree, and give priority to the links with larger residual capacity. Then in the external level, we aim to reduce the total number of occupied devices and increase the total backup flow. We leverage Chebyshev scalarization function based on pseudo‐random proportional rule to simplify weight selection, and enforce exploration to avoid falling into local optimum. We design the vector of rewards for different objectives, and update Pareto approximate set by multiple state steps to approach the optimal solution. Our strategy solves the weight selection problem successfully and achieves lower energy consumption.
Predicting Range of Initial Warfarin Dose Based on Pharmacometabolomic and Genetic Inputs
Authors: Huang Qing , Cao Ling , Luo Nan , Qian Hanyu , Wei Meng , Xue Ling , Zhou Qiang , Zou Bingjie , Tan Li , Chu Yanan , Ma Xueping , Wang Changtian , Wu Haiwei , Zhang Lei , Sun Lei , Li Demin , Fan Xialei , Miao Liyan , Zhou Guohua
Published: August 2021

Anticoagulation response to warfarin during the initial stage of therapy varies among individuals. In this study, we aimed to combine pharmacometabolomic and pharmacogenetic data to predict interindividual variation in warfarin response, and, on this basis, suggest an initial daily dose range. The baseline metabolic profiles, genotypes, and clinical information of 160 patients with heart valve disease served as the variables of the function of the last international normalized ratio measured before a patient’s discharge (INRday7) to screen for potential biomarkers. The partial least‐squares model showed that two baseline metabolites (uridine and guanosine), one single‐nucleotide variation (VKORC1), and four clinical parameters (weight, creatinine level, amiodarone usage, and initial daily dose) had good predictive power for INRday7 (R2 = 0.753 for the training set, 0.643 for the test set). With these biomarkers, a machine learning algorithm (two‐dimensional linear discriminant analysis‐multinomial logit model) was used to predict the subgroups with extremely warfarin‐sensitive or less warfarin‐sensitive patients with a prediction accuracy of 91% for the training set and 90% for the test set, indicating that individual responses to warfarin could be effectively predicted. Based on this model, we have successfully designed an algorithm,“IniWarD,” for predicting an effective dose range in the initial 7‐day warfarin therapy. The results indicate that the daily dose range suggested by the IniWarD system is more appropriate than that of the conventional genotype‐based method, and the risk of bleeding or thrombus due to warfarin could thus be avoided.
Improving the foliar biofortification of broccoli with selenium without commercial quality losses
Authors: Muñoz Fernando Felipe , Stoffel María Micaela , Céccoli Gabriel , Trod Betiana Soledad , Daurelio Lucas Damian , Bouzo Carlos Alberto , Guevara María Gabriela
Published: August 2021

Selenium‐biofortified broccoli (Brassica oleracea L. var. italica Plenck) is an important source of micronutrients in a healthy human diet. Therefore, studies are needed on the commercial production of selenium‐enriched broccoli. We analyzed the effect of the foliar application of sodium selenate and sodium selenite in doses of 50 and 100 g ha−1 on the growth, photosynthetic parameters, selenium accumulation, and commercial quality of broccoli in two cultivars (‘Belstar’ and ‘Legend’) used for fresh crops market grown under field conditions. The application of both doses of selenate and the highest dose of selenite induced a significant increase in the head fresh weight (FW) only in cultivar Belstar. However, the dry matter content of the heads was not significantly affected by selenium or the cultivar of broccoli. In addition, the increase in the water use efficiency, mainly due to the reduction of the transpiration rate, could explain the significant increase in the head FW without modifying the head dry matter content in Belstar. On the other hand, selenium treatments before harvest maintained the green color and did not affect the firmness and diameter of the heads at harvest. The selenium content of the heads increased markedly in a dose‐dependent manner in both cultivars, with both selenium treatments. The results of this study indicate that the response to selenium treatments differs between broccoli cultivars and that the use of both selenium salts in foliar form would be a good strategy to obtain selenium‐enriched broccoli, without affecting the commercial quality of the heads.
Nutrient stream attenuation is altered by the duration and frequency of flow intermittency
Authors: Saltarelli Wesley Aparecido , Cunha Davi Gasparini Fernandes , Freixa Anna , Perujo Núria , López‐Doval Julio C. , Acuña Vicenç , Sabater Sergi
Published: August 2021

River flow intermittency affects physical and biological processes in lotic ecosystems, including nutrient attenuation and therefore water purification. We investigated the effect of river flow intermittency, including its duration and occurrence frequency, on the attenuation of dissolved inorganic nitrogen (DIN) and soluble reactive phosphorus (P‐PO43−). The net balances of each nutrient form were assessed in artificial streams colonized by biofilms and exposed to six treatments resulting from the combination of two flow intermittency durations (28 or 56 days) and three intermittency frequencies (one, two or four interruption episodes). The respective influences on the nutrient balances were assessed one and eight days after flow resumption, with negative or positive balances indicating net consumption or production, respectively. The P‐PO43− balances ranged from −50.3 to −15.7 μg P‐PO43− h−1 m−2, while for the components of DIN, they varied between −135.6 and −7.3 μg N‐NH4+ h−1 m−2 (ammonium), −1.4 and 4.2 μg N‐NO2− h−1 m−2 (nitrite) and −39.1 and 18.6 μg N‐NO3− h−1 m−2 (nitrate). In general, longer non‐flow durations impaired nutrient attenuation. Overall, while each nutrient form showed specific patterns, our experiment indicated that (1) nutrient attenuation usually decreased with longer non‐flow durations, (2) attenuation generally recovered after frequent events of water flow resumption and when rewetting was longer and (3) longer desiccation periods seemed to persistently affect the biogeochemical responses regardless the number of times flow returned to the system. Our results highlight that more severe conditions (causing dehydration of the substrates and inhibition of biofilm activity) might strongly affect the biogeochemical functioning of temporary streams, with important management implications under accelerating global changes.
Bimetal Organic Framework Derived Atomically Dispersed Mn and N Codoped Porous Carbon for Efficient Oxygen Reduction
Authors: Yang Yanan , Sun Chaoyong , Zhang Huabing , Ke Shaojie , Liu Haitao , Dou Meiling , Wang Feng
Published: August 2021

Developing cost‐effective non‐precious metal electrocatalysts (NPMCs) for the sluggish oxygen reduction reaction (ORR) is critical for the large‐scale application of metal‐air battery and fuel cell technologies. Herein, we present an effective Mn/Zn bimetal organic frameworks (MOFs)‐based strategy to synthesize an efficient manganese (Mn) and nitrogen (N) co‐doped porous carbon electrocatalyst with atomically dispersed N‐coordinated single Mn moieties (Mn‐Nx) for ORR catalysis. This strategy involves the adsorption of Mn ions into the Mn/Zn bimetal MOFs followed by the subsequent pyrolysis in Ar and then activation in NH3. Owing to the atomically dispersed Mn‐Nx sites, the large specific surface area and the high content of graphitic‐N, the resulting electrocatalyst shows a superior ORR activity with a half‐wave potential of 0.885 V and an outstanding electrochemical durability in alkaline electrolyte outperforming commercial Pt/C, and it also exhibits a superior performance for an assembled primary Zn–air battery. This work offers a new prospect for the synthesis of MOFs‐derived highly efficient NPMCs for ORR.
New Paradigms in Porous Framework Materials for Acetylene Storage and Separation
Authors: Verma Gaurav , Ren Junyu , Kumar Sanjay , Ma Shengqian
Published: August 2021

Acetylene is an important precursor in the petrochemical, plastics and electronic industries, as well as the prominent fuel for welding and metal cutting. The high flammability and explosive nature of acetylene, however hinder its safe storage and transportation. Porous materials are highly promising for acetylene storage and as they can provide strong binding interactions and an optimal pore environment. Furthermore, high selectivity and separation can be achieved for acetylene over other gases such as CO2and small hydrocarbons. In this review, we divulge into the recent advancements and paradigms in acetylene storage and separation with a focus on porous metal‐organic frameworks (MOFs). An overview of the benchmark materials for acetylene storage and separation, along with some recent developments in the strategies to balance the trade‐off between the uptake capacity and selectivity is provided. The approaches of designing small pores and highly functionalized pore environments for strong binding with the acetylene adsorbate; along with the pore space partition, window space directed assembly and inverse CO2/C2H2adsorption for the separation of acetylene from CO2, CH4, C2H4and other hydrocarbons are reviewed to provide a summary and help further augment the research in this direction.
Whatisn'tsocial tolerance?The past, present, and possible future of an overused term in the field of primatology
Authors: DeTroy Sarah E. , Haun Daniel B. M. , van Leeuwen Edwin J. C.
Published: August 2021

In the past four decades, the termsocial tolerancehas been utilized to describe, explain, and predict many different aspects of primates' sociality and has been measured with a large range of traits and behaviors. To date, however, there has been little discussion on whether these different phenomena all reflect one and the same construct. This paper opens the discussion by presenting the historical development of the term social tolerance and a structured overview of its current, overextended use. We argue that social tolerance has developed to describe two distinct concepts: social tolerance as the social structure of a group and social tolerance as the dyadic or group‐level manifestation of tolerant behaviors. We highlight how these two concepts are based on conflicting theoretical understandings and practical assessments. In conclusion, we present suggestions for future research on primate social tolerance, which will allow for a more systematic and comparable investigation of primate sociality.
Cryptic TCF3 fusions in childhood leukemia: Detection by RNA sequencing
Authors: Salim Mustafa , Heldt Frederik , Thomay Kathrin , Lentes Jana , Behrens Yvonne Lisa , Kaune Beate , Möricke Anja , Cario Gunnar , Schieck Maximilian , Hofmann Winfried , Davenport Claudia , Steinemann Doris , Schrappe Martin , Schlegelberger Brigitte , Göhring Gudrun
Published: August 2021

Acute lymphoblastic leukemia (ALL) is the most frequent malignancy in childhood and adolescence. In more than 60% of cases of this heterogeneous disease, a genetic marker is identified via cytogenetic or molecular analyses. TCF3 gene fusions occur in 5%–11% of ALL patients. In < 1%, the TCF3 alteration in ALL leads to a TCF3‐HLF fusion gene. Even though this is a very rare event, the detection of a TCF3‐HLF fusion gene is associated with a very poor prognosis with incurable relapses in almost all patients. The frequent TCF3‐PBX1 fusion gene, which is detectable in 5%–10% of childhood B‐cell precursor ALLs and ~3.8% of adult B‐cell precursor ALLs, is associated with a rather good prognosis, that is, an observed event‐free 5‐year survival of approximately 85%. Thus, the distinction of the different partner genes fused to TCF3 is essential for risk assessment. To verify RNA sequencing as a tool for detection of known and unknown fusion genes, we screened 200 cases of pediatric B‐cell precursor ALL with “targeted” RNA sequencing in a pilot project in comparison to classical cytogenetic analyses (chromosome R‐banding analysis), fluorescence in situ hybridization, and PCR. We observed a TCF3 fusion gene in 6.5% (13/200) of the patients. Ten (5%) patients displayed a TCF3‐PBX1 fusion gene, two (1%) patients a TCF3‐FLI1 fusion gene, and one (0.5%) patient a TCF3‐HLF fusion gene. For the TCF3 fusions, we obtained discrepant results with the different methods, which are described in the article. Taken together, translocations leading to TCF3 fusion genes might appear cryptic and may remain undetected by a single method.
Musicianship and melodic predictability enhance neural gain in auditory cortex during pitch deviance detection
Authors: Quiroga‐Martinez David R. , Hansen Niels Christian , Højlund Andreas , Pearce Marcus , Brattico Elvira , Holmes Emma , Friston Karl , Vuust Peter
Published: August 2021

When listening to music, pitch deviations are more salient and elicit stronger prediction error responses when the melodic context is predictable and when the listener is a musician. Yet, the neuronal dynamics and changes in connectivity underlying such effects remain unclear. Here, we employed dynamic causal modeling (DCM) to investigate whether the magnetic mismatch negativity response (MMNm)—and its modulation by context predictability and musical expertise—are associated with enhanced neural gain of auditory areas, as a plausible mechanism for encoding precision‐weighted prediction errors. Using Bayesian model comparison, we asked whether models with intrinsic connections within primary auditory cortex (A1) and superior temporal gyrus (STG)—typically related to gain control—or extrinsic connections between A1 and STG—typically related to propagation of prediction and error signals—better explained magnetoencephalography responses. We found that, compared to regular sounds, out‐of‐tune pitch deviations were associated with lower intrinsic (inhibitory) connectivity in A1 and STG, and lower backward (inhibitory) connectivity from STG to A1, consistent with disinhibition and enhanced neural gain in these auditory areas. More predictable melodies were associated with disinhibition in right A1, while musicianship was associated with disinhibition in left A1 and reduced connectivity from STG to left A1. These results indicate that musicianship and melodic predictability, as well as pitch deviations themselves, enhance neural gain in auditory cortex during deviance detection. Our findings are consistent with predictive processing theories suggesting that precise and informative error signals are selected by the brain for subsequent hierarchical processing.
Knowledge and perceptions around self‐management of type 2 diabetes among a Sudanese community in Australia: A qualitative study
Authors: Roth Phoebe , Tang Clarice Y. , Rumbold Bruce , Gupta Sabrina
Published: August 2021

Issue addressed

People from Sudanese background are more likely to be diagnosed with type 2 diabetes (T2D) as compared to the general population. In recent years, there has been an increase in the number of migrants from Sudan to Australia. However, there is a dearth of research exploring the perceptions and experiences of self‐management strategies for diabetes among this migrant Sudanese population residing in Australia. This study aims to explore these experiences and perceptions as well as to identify cultural aspects related to T2D self‐management strategies for people from this migrant group.

Methods

A qualitative study using semi‐structured in‐depth interviews with Sudanese participants (n = 12) living with T2D was conducted in Melbourne, Australia.

Results

The thematic analysis found barriers to self‐management of diabetes to include language differences, the burden of self‐management, difficulties in accommodating traditional dietary practices in self‐management, as well as the expectations of familial and social obligations. Enablers included positive relationships with health professionals, support networks, involvement in religion and adopting traditional remedies.

Conclusions

This study found cultural considerations, such as incorporating traditional dietary practices and familial obligations into self‐management, to be the most significant influence for this group of Sudanese participants in the way they managed their diabetes.

So what

This study highlights the need for culturally appropriate provision of health services and resources for Sudanese people with T2D while recognising the value placed on traditional food choices. Importantly, the collectivist Sudanese culture must be considered for any future development and implementation of health promotion strategies.
Performance of DNA methylation‐based biomarkers in the cervical cancer screening program of northern Portugal: A feasibility study
Authors: Salta Sofia , Maia‐Moço Leonardo , Estevão‐Pereira Helena , Sequeira José Pedro , Vieira Renata , Bartosch Carla , Petronilho Sara , Monteiro Paula , Sousa Ana , Baldaque Inês , Rodrigues Jéssica , Sousa Hugo , Tavares Fernando , Henrique Rui , Jerónimo Carmen
Published: August 2021

Cervical cancer remains a health concern. Effective screening programs are critical to reduce the incidence and mortality. High‐risk HPV (hr‐HPV) testing as primary screening tool discloses high sensitivity but suboptimal specificity. Adequate triage tests to reduce unnecessary colposcopy referrals and overdiagnosis/overtreatment are crucial. Hence, we aimed to validate a panel of DNA methylation‐based markers as triage test for women hr‐HPV+ in the population‐based Regional Cervical Cancer Screening Program of Northern Portugal. Firstly, CADM1, MAL, FAM19A4 and hsa‐miR124‐2 promoter methylation levels were assessed by multiplex QMSP in a testing set of 402 FFPE tissue samples (159 normal samples and 243 cervical lesions, including 39 low‐grade intraepithelial squamous lesions [LSIL], 59 high‐grade intraepithelial squamous lesions [HSIL] and 145 cancerous lesions). Then, preliminary validation was performed in 125 hr‐HPV+ cervical scrapes (including 59 normal samples, 30 LSIL, 34 HSIL and 2 cancerous lesions). Higher MALme, FAM19A4me and hsa‐miR124‐2me methylation levels were disclosed in histological HSIL or worse (HSIL+) in testing set. Individually, markers depicted over 86% specificity for HSIL+ detection. In validation set, all these genes significantly differed between histological HSIL+ and low‐grade squamous intraepithelial lesions or less. In combination, these markers reached 74% specificity and 61% sensitivity for identification of histological HSIL+. We concluded that host gene methylation might constitute a useful referral triage tool of hr‐HPV+ women enrolled in the Cervical Cancer Screening Program of Northern Portugal.
Metabolic checkpoints and novel approaches for immunotherapy against cancer
Authors: Li Yiming , Tang Juan , Jiang Jianli , Chen Zhinan
Published: August 2021

While immunotherapy has achieved unprecedented success in conquering cancer, the majority of patients develop primary or acquired resistance to immunotherapy, largely in part due to the complicated metabolic networks in the tumor microenvironment. The microenvironmental metabolic networks are woven by a set of metabolic checkpoints, and accumulating evidence indicates that these metabolic checkpoints orchestrate antitumor immunity and immunotherapy. Metabolic checkpoints can regulate T cell development, differentiation and function, orchestrate metabolic competition between tumor cells and infiltrating T cells, and respond to the metabolic stress imposed on the infiltrating T cells. Furthermore, metabolic checkpoints and pathways can modulate the expression profiles of immune checkpoint receptors and ligands and vice versa. Therefore, repurposing interventions targeting metabolic checkpoints might synergize with immunotherapy, and promising approaches to reprogram the metabolic environment are much more warranted. In this review, we summarize recent researches on the metabolic checkpoints and discuss how these metabolic checkpoints regulate antitumor immunity and the promising approaches to modulate these metabolic checkpoints in the combination therapy. A comprehensive and objective understanding of the metabolic checkpoints might help the research and development of novel approaches to antitumor immunotherapy.
The implementation of CDK 4/6 inhibitors and its impact on treatment choices in HR+/HER2− advanced breast cancer patients: A study of the Dutch SONABRE Registry
Authors: Meegdes Marissa , Geurts Sandra M. E. , Erdkamp Frans L. G. , Dercksen Marcus Wouter , Vriens Birgit E. P. J. , Aaldering Kirsten N. A. , Pepels Manon J. A. E. , van de Winkel Linda M. H. , Teeuwen Nathalie J. A. , de Boer Maaike , Tjan‐Heijnen Vivianne C. G.
Published: August 2021

In August 2017, cyclin‐dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have been reimbursed in the Netherlands for patients with hormone receptor positive (HR+), HER2 negative (HER2−) advanced breast cancer (ABC). This study evaluates the implementation of CDK4/6 inhibitors and changes in treatment choices in the Netherlands. All patients diagnosed with HR+/HER2− ABC in 2009 to 2018 in seven hospitals were selected from the Southeast Netherlands Advanced Breast cancer (SONABRE) registry. The 2‐year cumulative use of CDK4/6 inhibitors since reimbursement date (August 2017) was assessed using competing‐risk methodology in two cohorts. The first cohort included patients with ABC diagnosis between August 2017 and December 2018. The second cohort included patients with ABC diagnosis between 2009 and August 2017, and still alive on August 1, 2017. In addition, treatment choices in the first three lines of therapy in calendar years 2009 to 2018 were evaluated for the total study population. Among patients diagnosed since August 2017 (n = 214), 50% (95% confidence interval [CI] = 43‐57) received CDK4/6 inhibitors within 2 years beyond diagnosis. Of eligible patients diagnosed before August 2017 (n = 417), 31% (95% CI = 27‐36) received CDK4/6 inhibitors within 2 years following reimbursement. Another 20% of both cohorts are still CDK4/6 inhibitor naïve and on first‐line therapy. The use of chemotherapy decreased in first two lines of therapy between 2009 and 2018 (first‐line: 29%‐13%; second‐line: 26%‐19%). The implementation rate of CDK4/6 inhibitors since reimbursement is currently 50% within 2 years beyond diagnosis and is expected to increase further. The implementation of targeted therapy decreased the use of chemotherapy as first‐line therapy.
Private lenders and borrowers’ internal control weaknesses
Authors: Hasan Md Mahmudul
Published: August 2021

This study examines whether the presence of private lenders is associated with the effectiveness of borrowers’ internal controls. I provide evidence that the presence of private lenders is an important determinant of internal control weaknesses in borrower firms. To monitor loan contracts, lenders use borrowers’ financial information, reliability of which to a great extent depends on the effectiveness of borrowers’ internal controls. I argue that lenders are likely to influence borrowers to maintain effective internal controls so that they can reliably use borrowers’ financial reporting information. Using a battery of tests, I find that the presence of private lenders has a significant negative association with the probability of borrowers’ disclosing a material weakness in internal controls.
Schizophrenia, the self and psychotherapy: Is there really anything new under the sun?
Authors: Lysaker Paul H.
Published: August 2021

Introduction

This issue of In Session in The Journal of Clinical Psychology offers in depth case studies of psychotherapy for persons with differing types of schizophrenia spectrum disorders across international settings.

Method

To understand the context and import of this work, this commentary explores commonalities of this work with past work including respect for patients' autonomy, compassion, and attention to the therapeutic relationship. The commentary then discusses themes which harken to the past including framing psychosis as something than can be understood jointly by therapist and patient rather than being unilaterally imposed.

Results

It is suggested that this work is emblematic of new movements in the literature which focus on the person who is experiencing schizophrenia.

Conclusions

This focus extends to understanding the purposes, place of the person in the world and their possibilities, which enables them to make sense of what they need and how want to manage their own recovery.
Trimethylamine N‐oxide exacerbates acetaminophen‐induced liver injury by interfering with macrophage‐mediated liver regeneration
Authors: Yan Mingzhu , Zhao Chong , Lu Shangyun , Cui Jinling , Sun Zhenou , Liu Xiaoyi , Liu Shuo , Huo Yazhen , Yin Shutao , Hu Hongbo
Published: August 2021

Acetaminophen (APAP)‐induced acute liver injury (AILI) is the most frequent cause of acute liver failure in developed countries. Trimethylamine N‐oxide (TMAO) is a metabolite derived from the gut microbiota and is relatively high in the circulation of the elderly, individuals with diabetes, and heart disease. Herein, we showed that TMAO exacerbates APAP hepatotoxicity. It is possible that delayed liver repair and regeneration that resulted from reduced macrophage accumulation was responsible for this combined hepatotoxicity. Moreover, matrix metalloproteinase 12 (Mmp12), expressed predominantly by macrophages, were reduced by TMAO in vitro and in vivo. This led to the inhibition of macrophage migration and a subsequent decrease in the recruitment of proresolving macrophages to the necrosis area. Furthermore, the administration of recombinant Mmp12 mitigated the enhanced hepatotoxicity in mice cotreated with TMAO and APAP. Overall, this study indicates that TMAO exacerbates APAP‐induced hepatotoxicity by hindering macrophage‐mediated liver repair, which might stem from the inhibition of Mmp12. These findings imply that liver damage in patients with high levels of circulating TMAO may be more severe in AILI and should exercise caution when treating with NAC.
Features of capsule endoscopy in COVID‐19 patients with a six‐month follow‐up: A prospective observational study
Authors: Xie Xiao‐Ping , Sheng Li‐Ping , Han Chao‐Qun , Jin Yu , Bai Tao , Lin Rong , Ding Zhen , Hou Xiao‐Hua
Published: August 2021

Recently, the coronavirus disease 2019 (COVID‐19) has caused a global pandemic. Several studies indicate that the digestive system can also be affected by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Therefore, patients with digestive symptoms should have a capsule endoscopy (CE). COVID‐19 patients with gastrointestinal (GI) symptoms who underwent CE were recruited from March 2020 to April 2020. We collected patients’ data and performed a prospective follow‐up study for 6 months. All 11 COVID‐19 cases with GI symptoms who underwent CE presented gastritis. Eight cases (72.7%) had intestinal mucosa inflammation. Among them, two cases showed intestinal ulcers or erosions. Moreover, two cases displayed colonic mucositis. One case was lost during follow‐up. At 3–6 months after hospital discharge, five patients underwent CE again, presenting gastrointestinal lesions. Five of the 10 cases had GI symptoms, such as abdominal pain, diarrhea, constipation, and others. Among these five cases, the GI symptoms of three patients disappeared at the last follow‐up and two patients still presented diarrhea symptoms. Overall, we observed damaged digestive tract mucosa that could be caused by SARS‐CoV‐2. Moreover, after discharge, some patients still presented intestinal lesions and GI symptoms.
Agroclimatic indices across the Canadian Prairies under a changing climate and their implications for agriculture
Authors: Chipanshi Aston , Berry Mark , Zhang Yinsuo , Qian Budong , Steier Garrett
Published: August 2021

With the objective of trying to understand the adaptability of agriculture across the Canadian Prairies under climate change, simple‐to‐use agroclimatic indices were calculated for the base climate period of 1981 to 2010 and for both the medium (RCP4.5) and high (RCP8.5) emission projections extending to the distant future (2071–2100). The agroclimatic indices included the Effective Growing Degree Days (EGDDs), Growing Season Length (GSL), the Climate Moisture Index (CMI), and the Temperature Humidity Index (THI). For climate change in 30‐year periods, these indices were calculated as multi‐model ensembles of six Global Climate Models recommended under the Coupled Model Intercomparison Project Phase 5 (CMIP5) for the study area. We found that the GSL, EGDDs, CMI, and THI were amplified above the values of the base climate period in the order of 40–50 days, 600–1200 heat units, −100 to −120 mm and 3–4 THI units by the close of the distant future (2071–2100) under the RCP4.5 and RCP8.5, respectively. This amplification has implications on where crop and livestock production could become more suitable or riskier in future. Opportunities include expanding crop and livestock production to more northerly regions which currently have insufficient heat units, a short growing season and unfavourable temperature humidity thresholds for livestock production. Moisture deficits will continue to be the greatest risk during the growing season under climate change scenarios but options exist to implement adaptive measures such as staggering seeding times to take advantage of moisture availability in the spring and autumn seasons and crop substitution. This study has relevance for policy and program formulation and implementation in Canada's agricultural regions and potentially, other areas of the world with similar climate change outcomes.
Preoperative neutrophil‐to‐lymphocyte ratio predicts the prognosis of esophageal squamous cell cancer patients undergoing minimally invasive esophagectomy after neoadjuvant chemotherapy
Authors: Kato Takashi , Oshikiri Taro , Goto Hironobu , Urakawa Naoki , Hasegawa Hiroshi , Kanaji Shingo , Yamashita Kimihiro , Matsuda Takeru , Nakamura Tetsu , Suzuki Satoshi , Kakeji Yoshihiro
Published: August 2021

Background

One of the primary treatment for resectable advanced esophageal squamous cell cancer (ESCC) is neoadjuvant chemotherapy (NAC) followed by minimally invasive esophagectomy (MIE). Because the neutrophil‐to‐lymphocyte ratio (NLR) is a widely reported prognostic factor in several cancers, we investigated whether the preoperative NLR is a biomarker in ESCC patients treated with NAC and MIE.

Methods

In this study, we investigated 174 ESCC patients who underwent MIE from January 2010 to December 2015, including 121 patients who received NAC. The cutoff value of the NLR was analyzed using the receiver operating characteristic curve. Multivariate analyses were performed to clarify independent prognostic factors for overall survival (OS).

Results

The cutoff value of the NLR for OS in 121 patients who received NAC was 2.5 ng/ml, and the area under the curve was 0.63026 (p = 0.0127). The 5‐year OS rate was 64% in those with an NLR <2.5 and 39% in those with an NLR ≥2.5. According to multivariate analysis, NLR ≥2.5, pathological T, pathological N, and intraoperative blood loss of >415 ml were independent poor prognostic factors.

Conclusions

NLR is a biomarker of prognosis in ESCC patients who undergo MIE after NAC.