bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving generalizability and study design of Alzheimer's disease cohort studies in the United States by including under‐represented populations
Authors: Mindt Monica Rivera , Okonkwo Ozioma , Weiner Michael W. , Veitch Dallas P. , Aisen Paul , Ashford Miriam , Coker Godfrey , Donohue Michael C. , Langa Kenneth M. , Miller Garrett , Petersen Ronald , Raman Rema , Nosheny Rachel
Published: November 2022

The poor generalizability of clinical research data due to the enrollment of highly educated, non‐Latinx White participants hampers the development of therapies for Alzheimer's disease (AD). Black and Latinx older adults have a greater risk for dementia, yet it is unclear how health‐care disparities and sociocultural factors influence potential AD therapies and prognosis. Low enrollment of under‐represented populations may be attributable to several factors including greater exclusion due to higher rates of comorbidities, lower access to AD clinics, and the legacy of unethical treatment in medical research. This perspective outlines solutions tested in the Brain Health Registry (BHR) and the Alzheimer's Disease Neuroimaging Initiative (ADNI), including culturally‐informed digital research methods, community‐engaged research strategies, leadership from under‐represented communities, and the reduction of exclusion criteria based on comorbidities. Our successes demonstrate that it is possible to increase the inclusion and engagement of under‐represented populations into US‐based clinical studies, thereby increasing the generalizability of their results.
Economical Access to Diverse Enantiopure Tetrahydropyridines and Piperidines Enabled by Catalytic Borrowing Hydrogen
Authors: Ng Teng Wei , Tao Ran , See Willy Wei Li , Poh Si Bei , Zhao Yu
Published: November 2022

We disclose herein a catalytic borrowing hydrogen method that enables an unprecedented, economical one‐pot access to enantiopure tetrahydropyridines with minimal reagent use or waste formation. This method couples a few classes of readily available substrates with commercially available 1,3‐amino alcohols, and delivers the valuable tetrahydropyridines of different substitution patterns free of N‐protection. Such transformations are highly challenging to achieve, as multiple redox steps need to be realized in a cascade and numerous side reactions including a facile aromatization have to be overcome. Highly diastereoselective functionalizations of tetrahydropyridines also result in a general access to enantiopure di‐ and tri‐substituted piperidines, which ranks the topmost frequent N‐heterocycle in commercial drugs.
Highly Reversible Zinc Metal Anode in a Dilute Aqueous Electrolyte Enabled by a pH Buffer Additive
Authors: Zhang Wei , Dai Yuhang , Chen Ruwei , Xu Zhenming , Li Jianwei , Zong Wei , Li Huangxu , Li Zheng , Zhang Zhenyu , Zhu Jiexin , Guo Fei , Gao Xuan , Du Zijuan , Chen Jintao , Wang Tianlei , He Guanjie , Parkin Ivan P.
Published: November 2022

Aqueous zinc‐ion batteries have drawn increasing attention due to the intrinsic safety, cost‐effectiveness and high energy density. However, parasitic reactions and non‐uniform dendrite growth on the Zn anode side impede their application. Herein, a multifunctional additive, ammonium dihydrogen phosphate (NHP), is introduced to regulate uniform zinc deposition and to suppress side reactions. The results show that the NH4+tends to be preferably absorbed on the Zn surface to form a “shielding effect” and blocks the direct contact of water with Zn. Moreover, NH4+and (H2PO4)−jointly maintain pH values of the electrode‐electrolyte interface. Consequently, the NHP additive enables highly reversible Zn plating/stripping behaviors in Zn//Zn and Zn//Cu cells. Furthermore, the electrochemical performances of Zn//MnO2full cells and Zn//active carbon (AC) capacitors are improved. This work provides an efficient and general strategy for modifying Zn plating/stripping behaviors and suppressing side reactions in mild aqueous electrolyte.
Umpolung Asymmetric 1,5‐Conjugate Addition via Palladium Hydride Catalysis
Authors: Wang Yu‐Chao , Xiao Zhao‐Xin , Wang Miao , Yang Shao‐Qian , Liu Jin‐Biao , He Zhi‐Tao
Published: November 2022

Electronically matched nucleophilic 1,6‐conjugate addition has been well studied and widely applied in synthetic areas. In contrast, nucleophilic 1,5‐conjugate addition represents an electronically forbidden process and is considered unfeasible. Here, we describe modular protocols for 1,5‐conjugate addition reactions via palladium hydride catalysis. Both palladium and synergistic Pd/organocatalyst systems are developed to catalyze 1,5‐conjugate reaction, followed by inter‐ or intramolecular [3+2] cyclization. A migratory 1,5‐addition protocol is established to corroborate the feasibility of this umpolung concept. The 1,5‐addition products are conveniently transformed into a series of privileged enantioenriched motifs, including polysubstituted tetrahydrofuran, dihydrofuran, cyclopropane, cyclobutane, azetidine, oxetane, thietane, spirocycle and bridged rings. Preliminary mechanistic studies corroborate the involvement of palladium hydride catalysis.
Mixed Matrix Membrane with Penetrating Subnanochannels: A Versatile Nanofluidic Platform for Selective Metal Ion Conduction
Authors: Li Chen , Jiang Yanan , Wu Zihan , Zhang Youcai , Huang Cheng , Cheng Sha , You Ya , Zhang Pengchao , Chen Wen , Mao Lanqun , Jiang Lei
Published: November 2022

Biological ion channels penetrated through cell membrane form unique transport pathways for selective ionic conductance. Replicating the success of ion selectivity with mixed matrix membranes (MMMs) will enable new separation technologies but remains challenging. Herein, we report a soft substrate‐assisted solution casting method to develop MMMs with penetrating subnanochannels for selective metal ion conduction. The MMMs are composed of penetrating Prussian white (PW) microcubes with subnanochannels in dense polyimide (PI) matrices, achieving selective monovalent metal ion conduction. The ion selectivity of K+/Mg2+is up to 14.0, and the ion conductance of K+can reach 45.5 μS with the testing diameter of 5 mm, which can be further improved by increasing the testing area. Given the diversity of nanoporous materials and polymer matrices, we expect that the MMMs with penetrating subnanochannels could be developed into a versatile nanofluidic platform for various emerging applications.
Cancer treatments touch a wide range of values that count for patients and other stakeholders: What are the implications for decision‐making?
Authors: Vrinzen Cilla E. J. , Bloemendal Haiko J. , Stuart Esra , Makady Amr , van Agthoven Michel , Koster Mariska , Merkx Matthias A. W. , Hermens Rosella P. M. G. , Jeurissen Patrick P. T.
Published: November 2022

Background

Cancer rates and expenditures are increasing, resulting in debates on the exact value of this care. Perspectives on what exactly constitutes worthwhile values differ. This study aims to explore all values–elements regarding new oncological treatments for patients with cancer and all stakeholders involved and to assess their implications in different decision‐making procedures.

Method

Thirty‐one individual in‐depth interviews were conducted with different stakeholders to identify values within oncology. A focus group with seven experts was performed to explore its possible implications in decision‐making procedures.

Results

The overarching themes of values identified were impact on daily life and future, costs for patients and loved ones, quality of life, impact on loved ones, societal impact and quality of treatments. The expert panel revealed that the extended exploration of values that matter to patients is deemed useful in patient‐level decision‐making, information provision, patient empowerment and support during and after treatment. For national reimbursement decisions, implications for the broad range of values seems less clear.

Conclusion

Clinical values are not the only ones that matter to oncological patients and the stakeholders in the field. We found a much broader range of values. Proper recognition of values that count might add to patient‐level decision‐making, but implications for reimbursement decisions are less clear. The results could be useful to guide clinicians and policymakers when it comes to decision‐making in oncology. Making more explicit which values counts for whom guarantees a more systematic approach to decision‐making on all levels.
Lawsuit over alleged sexual abuse by AT serves as cautionary tale
Authors: O'Brien Timothy
Published: November 2022

Reports of sexual abuse committed by certain team physicians against student‐athletes made headlines during the last few years, unfortunately demonstrating that male and female team members were at risk of being victimized by certain wayward physicians.
Don't let imposter syndrome hold you back
Authors: Hodges Dawn Z.
Published: November 2022

I received a text recently from a former colleague. She said, “I need a pep talk. My imposter syndrome is flaring up.” Dictionary.com defines imposter syndrome as “anxiety or self‐doubt that results from persistently undervaluing one's competence and active role in achieving success.”
A New Highly Oxygenated Polyketide Derivative from Trichoderma sp. and Its Antifungal Activity
Authors: Wang Cheng‐Yao , Gan Dong , Li Chen‐Zhe , Zhang Sheng‐Qi , Li Bin‐Xian , Zhu Li , Liu Jia‐Qi , Liu Han , Tuo Gui‐Tao , Zhang Feng‐Mei , Cai Le
Published: November 2022

A new highly oxygenated polyketide derivative, trichodersine (1), together with fourteen known compounds (2‐15) were isolated from Trichoderma sp. MWTGP‐04. The structure of trichodersine (1) was established based on comprehensive spectroscopic data analysis, and biogenesis argument. The results of double culture experiments indicated that the strain exhibited potential antifungal activity. The antifungal activities of all isolated compounds were evaluated, among them compound 1 exhibited remarkable antifungal activities against Fusarium solani, Plectosphaerella cucumerina, Alternaria panax, and Aspergillus niger, with minimum inhibitory concentrations (MICs) of 4, 4, 16, and 32 μg/mL, respectively. In addition, the antifungal experiments of polyketide derivatives (1–3) disclosed that their degree of oxidation was a key factor affecting the antifungal activity.
A New Capillary Gas Chromatography Column Based on Poly(ethylene glycol) Methyl Ether‐Functionalized Calix[4]arene
Authors: Chen Ruonan , Cai Zhiqiang , Li Wei , Huang Qiuchen , Nardiello Donatella , Quinto Maurizio , Liu Xianming , Hu Shaoqiang , Sun Tao
Published: November 2022

In this work, a novel capillary column (C4A‐mPEG) with a calixarene‐based polymer stationary phase (poly(ethylene glycol) methyl ether‐functionalized 4‐tert‐butylcalix[4]arene) was designed and used for gas chromatographic (GC) separations. The C4A‐mPEG capillary column, prepared by the static coating method, showed moderate polarity and a column efficiency of 2332 plates/m, determined by 1‐octanol at 120 °C. The separation features of C4A‐mPEG stationary phase, resulting from its unique structure and multiple molecular recognition processes with analytes, including π‐π, H‐bonding, dipole‐dipole, and van der Waals interactions, allowed to obtain high‐resolution performances for a wide range of compounds and their isomers, especially benzaldehydes, phenols, and anilines. Moreover, compared with 4‐tertbutyl calix[4]arene (C4A) and polyethylene glycol (PEG) stationary phases, a higher resolving capability was also observed for the separation of toluidine and xylidine isomers.
Comparing the Catalytic and Structural Characteristics of a ‘Short’ Unspecific Peroxygenase (UPO) Expressed in Pichia pastoris and Escherichia coli
Authors: Robinson Wendy X. Q. , Mielke Tamara , Melling Benjamin , Cuetos Anibal , Parkin Alison , Unsworth William P. , Cartwright Jared , Grogan Gideon
Published: November 2022

Unspecific peroxygenases (UPOs) have emerged as valuable tools for the oxygenation of non‐activated carbon atoms, as they exhibit high turnovers, good stability and depend only on hydrogen peroxide as the external oxidant for activity. However, the isolation of UPOs from their natural fungal sources remains a barrier to wider application. We have cloned the gene encoding an ‘artificial’ peroxygenase (artUPO), close in sequence to the ‘short’ UPO from Marasmius rotula (MroUPO), and expressed it in both the yeast Pichia pastoris and E. coli to compare the catalytic and structural characteristics of the enzymes produced in each system. Catalytic efficiency for the UPO substrate 5‐nitro‐1,3‐benzodioxole (NBD) was largely the same for both enzymes, and the structures also revealed few differences apart from the expected glycosylation of the yeast enzyme. However, the glycosylated enzyme displayed greater stability, as determined by nano differential scanning fluorimetry (nano‐DSF) measurements. Interestingly, while artUPO hydroxylated ethylbenzene derivatives to give the (R)‐alcohols, also given by a variant of the ‘long’ UPO from Agrocybe aegerita (AaeUPO), it gave the opposite (S)‐series of sulfoxide products from a range of sulfide substrates, broadening the scope for application of the enzymes. The structures of artUPO reveal substantial differences to that of AaeUPO, and provide a platform for investigating the distinctive activity of this and related'short’ UPOs.
Thermal Transport and Thermoelectric Properties of Rb2PdX6 (X=Cl, Br) from First‐principles Study
Authors: Liu Rongkun , Hu Yanxiao , Feng Chunbao , Ding Guangqian , Zhang Gang , Li Dengfeng
Published: November 2022

Vacancy‐ordered double perovskites are characterized by stable structure, non‐toxicity, low thermal conductivity, and large Seebeck coefficient, which are potential thermoelectric materials. In this work, the thermal transport and thermoelectric properties of Rb2PdX6(X=Cl, Br) are theoretically investigated. We find that the calculated thermal conductivity is underestimated from the phonon Boltzmann transport equation (PBTE) since the mean free path of a large number of phonons is less than the Ioffe‐Regel limit. The room‐temperature thermal conductivities of Rb2PdCl6 and Rb2PdBr6 are 0.42 W m−1 K−1 and 0.22 W m−1 K−1 based on two‐channel phonon transport mode, respectively. The thermal conductivity of Rb2PdBr6 is almost unchanged with the temperature. Rb2PdX6(X=Cl, Br) have large Seebeck coefficient for p‐type doping due to triple degeneracy in the VBM and the thermoelectric property of p‐type doping is better than that for n‐type doping. The ab initio scattering and transport program (AMSET) is used to calculate the electron scattering rate. At 700 K, the maximum ZT of p‐type doping Rb2PdCl6 and Rb2PdBr6 can reach to 0.51 and 1.31, respectively. Replacement of Cl by Br results in lower thermal conductivity and smaller bandgap, and thus larger the maximum ZT value. This work demonstrates that Rb2PdBr6 is a potential high‐performance p‐type thermoelectric perovskite material.
Preparation and Application of Nanozymes with Uricase‐Like Activity Based on Molecularly Imprinted Polymers
Authors: Liu Donghao , Yi Simin , Ni Xu , Zhang Jingjing , Wang Fangqi , Yang Ping , Liu Meiru , Peng Jun , Dramou Pierre , He Hua
Published: November 2022

Nanozymes have advantages over natural enzymes in terms of efficiency, stability, and economy. MVSM (Mixed Valence State MOF) is a nano‐oxidase with uricase‐like activity that may catalyze uric acid (UA) in the body into allantoin and H2O2 to treat gout and hyperuricemia by substituting natural uricase. However, it cannot specifically identify and choose UA. To increase the selectivity and affinity of MVSM for UA, the composite material MVSM@MIP is innovatively synthesized using a new synthetic approach termed the “two‐step synthesis method,” which may prevent UA from being oxidized by MVSM during manufacture in this study. At the same time, this study also provides experimental proof of the effective creation of the material, the advantages of the “two‐step synthesis approach,” and the high selectivity and affinity of MVSM@MIP for UA. Based on these findings, the suggested technique may be used to effectively catalyze uric acid in human urine with high activity.
Prescriber Adoption of SLCO1B1Genotype‐Guided Simvastatin Clinical Decision Support in a Clinical Pharmacogenetics Program
Authors: Obeng Aniwaa Owusu , Scott Stuart A. , Kaszemacher Tom , Ellis Stephen B. , Mejia Ana , Gomez Alanna , Nadukuru Rajiv , Abul‐Husn Noura S. , Vega Aida , Waite Eva , Gottesman Omri , Cho Judy , Bottinger Erwin P.
Published: November 2022

Pharmacogenetic implementation programs are increasingly feasible due to the availability of clinical guidelines for implementation research. The utilization of these resources has been reported with selected drug–gene pairs; however, little is known about how prescribers respond to pharmacogenetic recommendations for statin therapy. We prospectively assessed prescriber interaction with point‐of‐care clinical decision support (CDS) to guide simvastatin therapy for a diverse cohort of primary care patients enrolled in a clinical pharmacogenetics program. Of the 1,639 preemptively genotyped patients, 298 (18.2%) had an intermediate function (IF) OATP1B1 phenotype and 25 (1.53%) had a poor function (PF) phenotype, predicted by a common single nucleotide variant in the SLCO1B1 gene (c.521T>C; rs4149056). Clinicians were presented with CDS when simvastatin was prescribed for patients with IF or PF through the electronic health record. Importantly, 64.2% of the CDS deployed at the point‐of‐care was accepted by the prescribers and resulted in prescription changes. Statin intensity was found to significantly influence prescriber adoption of the pharmacogenetic‐guided CDS, whereas patient gender or race, prescriber type, or pharmacogenetic training status did not significantly influence adoption. This study demonstrates that primary care providers readily adopt pharmacogenetic information to guide statin therapy for the majority of patients with preemptive genotype data.
Enhanced Optical and Electrical Interactions at the Pt/MgSe Interfaces Designed for 6G Communication Technology
Authors: Algarni Sabah E. , Qasrawi A. F. , Khusayfan Najla M.
Published: November 2022

Magnesium selenide thin films are coated onto glass and semitransparent Pt substrates (nanosheets) by the vacuum evaporation technique under a vacuum pressure of 10−5 mbar. The effect of Pt nanosheets of thicknesses of 100 nm on the structural, compositional, optical, and electrical properties of MgSe is explored. It is found that platinum nanosheets enhance the light absorbability in the visible and infrared ranges of light. They slightly redshift the energy bandgap and decrease the dielectric constant. The strong interaction between Pt and MgSe increases the electrical conductivity by five orders of magnitude. Pt forms shallow impurity levels in the energy bandgap of MgSe allowing the tunneling process at the Pt/MgSe interfaces. Practically, a Pt/MgSe/Pt tunneling type device is fabricated and tested by the microwave impedance spectroscopy technique. It is found that Pt/MgSe/Pt devices can exhibit resonance–antiresonance and negative capacitance effects which are important in electronic circuits as parasitic capacitance cancelers, signal amplifiers, and noise reducers. In addition, evaluation of the cutoff frequency spectra has shown the ability of using the Pt/MgSe/Pt devices as microwave resonators appropriate for 5G/6G technologies. A cutoff frequency larger than 70 GHz can be achieved by imposing ac signal of amplitude of 0.10 V.
Hydrogeological feasibility of mine water deep geological storage in Baotashan coarse sandstone: A case study in Ordos Basin
Authors: Chen Ge , Sun Yajun , Xu Zhimin , Li Xin
Published: November 2022

For the sake of mine water drainage and sustainable groundwater protection, the new approach of mine water deep geological storage (MWDGS) is highly necessary to save water resources in the semi‐arid region of China. However, up to now, little academic research has been done on mine water geological storage. Given this situation, the hydrogeological feasibility of MWDGS was explored in Baotashan coarse sandstone (BCS) of Jurassic measure in Ordos Basin. The results show that the white‐gray BCS with a fragile skeleton of quartz (41.4%), feldspar (21.1%), and clay minerals (16.4%) provides the potential variable‐void for mine water; and its hydro‐chemical type of BCS aquifer is CO3‐Na and Cl‐Na. As the burial depth increases, the strong alkaline groundwater is in stagnant and poor recharge‐runoff‐discharge condition. The lab test shows that the pores whose diameter is over 10 μm could be treated as the main storage of mine water; and the effective porosity varies from 1.36% to 3.46%. When mine water is injected, the strong hydrodynamics of mine water storage would change the permeability significantly and about 0.201% soluble solids would be dissolved. Partial clay minerals obstruct the pores and induce the saturated phase of high permeability to evolve into steady phase of lower permeability. Under the condition of nonhydraulic fracturing during continuous storage, the heterogeneous anisotropic medium obtained by Transition PRObability GeoStatistics (TPROGS) shows that the capacity of BCS aquifer is 0.455 to 1.226 Mm3 for 1 km2 in the study area. The simulation shows that the groundwater mound in well‐scale and mine‐scale would be formed. The groundwater quality characteristics of “Three Zone” would occur around and gradually drop to approximate the original brine within 10 years. The hydrogeological feasibility reveals that this approach is useful for the well design and groundwater environment management during the mine water deep geological storage project in the Ordos basin.
Electrochemical Method for G‐quartet RNA Detection of COVID‐19 Based on Cyclic Ferrocenylnaphthalene Diimide
Authors: Kaneyoshi Shuma , Murakami Shun , Ikeda Takumi , Fujimoto Kazuhisa , Fujii Satoshi , Sato Shinobu , Takenaka Shigeori
Published: November 2022

To develop an electrochemical detection method for COVID‐19, we have investigated the interaction between RG‐1, a characteristic parallel four‐strand RNA component of the COVID‐19 genome, and cyclic ferrocenylnaphthalene diimides carrying different linker lengths 1 and 2, which bind to RG‐1 more strongly than cyclic naphthalene diimide 3 that lacks a ferrocene moiety. In particular, the binding affinity of 1 having short one showed the highest binding affinity to RG‐1, and the redox current of 1 increased in the presence of RG‐1 using a glassy carbon electrode. This increasing current of 1 in the presence of c‐myc as a parallel G4 DNA or single‐stranded RNA was lower than that in the presence of RG‐1. Several RG‐1 was electrochemically detected at the nanomolar level by 1.
Nomograms as a graphical model to predict biogas at municipal wastewater treatment plant using fuzzy indices
Authors: Anaokar Guruprasad S. , Khambete Anjali K. , Christian Robin A.
Published: November 2022

The strength of municipal wastewater and sludge considering their potential for biogasification can be expressed in terms of multiple parameter comprehensive indices (MPCI), namely, Wastewater Comprehensive Index (WWCI) and Sludge Comprehensive Index (SCI), respectively. Both of these indices can be calculated using fuzzy multiple criteria decisions making (FMCDM). Simple linear equations are established to express the relation between these indices, suspended solids concentration and biogas. The linear equation is developed to predict biogas from multiple parameter comprehensive indices, which indicate the linear relation between strength of wastewater, sludge and biogas. Nomogram was developed to get immediate quantification of biogas by linear scaling of suspended solid concentration and multiple parameter comprehensive indices (MPCI). Using a linear equation obtained from regression analysis; a suitable scale was developed to construct the nomogram. The biogas was found 96% precise with reference to measured one when estimated using nomograms. A single parameter, that is, suspended solids concentration will be monitored at municipal wastewater treatment plant, by digital device; to save chemicals, time, power and human resource. While taking efforts toward smart cities; digitalization and resource conservation will be creditable.
Evaluation of patient transport service in hospitals using process mining methods: Patients' perspective
Authors: Kropp Tobias , Faeghi Shiva , Lennerts Kunibert
Published: November 2022

Designing healthcare facilities and their processes is a complex task which influences the quality and efficiency of healthcare services. The ongoing demand for healthcare services and cost burdens necessitate the application of analytical methods to enhance the overall service efficiency in hospitals. However, the variability in healthcare processes makes it highly complicated to accomplish this aim. This study addresses the complexity in the patient transport service process at a German hospital, and proposes a method based on process mining to obtain a holistic approach to recognise bottlenecks and main reasons for delays and resulting high costs associated with idle resources. To this aim, the event log data from the patient transport software system is collected and processed to discover the sequences and the timeline of the activities for the different cases of the transport process. The comparison between the actual and planned processes from the data set of the year 2020 shows that, for example, around 36% of the cases were 10 or more minutes delayed. To find delay issues in the process flow and their root causes the data traces of certain routes are intensively assessed. Additionally, the compliance with the predefined Key Performance Indicators concerning travel time and delay thresholds for individual cases was investigated. The efficiency of assignment of the transport requests to the transportation staff are also evaluated which gives useful understanding regarding staffing potential improvements. The research shows that process mining is an efficient method to provide comprehensive knowledge through process models that serve as Interactive Process Indicators and to extract significant transport pathways. It also suggests a more efficient patient transport concept and provides the decision makers with useful managerial insights to come up with efficient patient‐centred analysis of transportation services through data from supporting information systems.
Strengthening rural surgery in the Philippines: Essential in achieving universal health care
Authors: Viray Brent A. G. , Arcilla Crisostomo E. , Perez Anthony R. , Marfori Jose R. , De Leon Michael , Ahmadi Attaullah , Lucero‐Prisno Don E.
Published: November 2022

The Lancet Commission on Global Surgery (LCoGS) launched Global Surgery 2030 to address the surgical services inequities with a bias toward low‐income and middle‐income countries like the Philippines. The same inequity is observed particularly when it comes to the urban‐rural divide. With more than half of the population living in rural areas, access to surgery becomes a major challenge that further impedes the much‐needed health of an economically productive workforce. The Universal Health Care [UHC] Act (RA 11332) of 2019 ensures that all Filipinos have access to quality, cost‐effective, promotive, preventive, curative, rehabilitative, and palliative health services without causing a financial burden. Recognizing the provision of essential surgery, in the context of primary healthcare is important. It should be accessible, continuous, comprehensive, and coordinated at the time of need – parallel to the principle of primary health care. Driven by this concept and experiences, the authors conceptualized and presented the Philippine Rural Surgery model for future development and implementation. This is envisioned to provide essential surgery among local rural primary health care settings that is universal, accessible, cost‐effective and safe. As this is still new in the Philippines, we proposed tenets and recommendations based on WHO Health System Strengthening building blocks to guide stakeholders in creating formal plans towards institutionalization under the principles of UHC. Such access to surgical service in the context of a unique socio‐demography of the Philippines would be essential in attaining the parameters and provisions set by the UHC Act.
Magnetohydrodynamic chemically reactive viscoelastic fluid flow through an inclined porous layer
Authors: Das Utpal J.
Published: November 2022

Analysis of a time‐independent magnetohydrodynamic viscoelastic fluid flow in a deformable inclined porous layer with first‐order chemical reaction has been investigated. Walters' fluid model has been used to study viscoelastic fluid. The walls are suctioned/injected at a constant rate. The expression representing the solution for solid displacement, fluid velocity, temperature, and concentration distribution is obtained. The effect of applicable parameters on solid displacement, fluid velocity, temperature, and concentration are discussed graphically, while skin friction, heat transfer, and mass transfer are revealed in a tabular structure. It is noticed that solid displacement, fluid velocity, and temperature profiles decrease when the viscoelastic parameter increase. Solid displacement enhances and the velocity of the fluid reduces owing to the influence of increasing drag parameter, whereas the reverse effect is seen for the volume fraction parameter. Nusselt number at the walls shows the opposite behavior for the viscoelastic parameter and Eckert number. Sherwood number at the walls shows opposite behavior for Reynolds number, Schmidt number, and radiation parameter. Also, the entropy generation number rises as a result of the influence of viscoelasticity and Eckert number.
Bone marrow stromal cells are sensitive to discrete surface alterations in build and post‐build modifications of bioinspired Ti6Al4V 3D‐printed in vitro testing constructs
Authors: Berger Michael B. , Cohen D. Joshua , Snyder Kyle , Sions John , Boyan Barbara D. , Schwartz Zvi
Published: November 2022

Current standards in bone‐facing implant fabrication by metal 3D (M3D) printing require post‐manufacturing modifications to create distinct surface properties and create implant microenvironments that promote osseointegration. However, the biological consequences of build parameters and surface modifications are not well understood. This study evaluated the relative contributions of build parameters and post‐manufacturing modification techniques to cell responses that impact osseointegration in vivo. Biomimetic testing constructs were created by using a M3D printer with standard titanium–aluminum–vanadium (Ti6Al4V) print parameters. These constructs were treated by either grit‐blasting and acid‐etching (GB + AE) or GB + AE followed by hot isostatic pressure (HIP) (GB + AE, HIP). Next, nine constructs were created by using a M3D printer with three build parameters: (1) standard, (2) increased hatch spacing, and (3) no infill, and additional contour trace. Each build type was further processed by either GB + AE, or HIP, or a combination of HIP treatment followed by GB + AE (GB + AE, HIP). Resulting constructs were assessed by SEM, micro‐CT, optical profilometry, XPS, and mechanical compression. Cellular response was determined by culturing human bone marrow stromal cells (MSCs) for 7 days. Surface topography differed depending on processing method; HIP created micro‐/nano‐ridge like structures and GB + AE created micro‐pits and nano‐scale texture. Micro‐CT showed decreases in closed pore number and closed porosity after HIP treatment in the third build parameter constructs. Compressive moduli were similar for all constructs. All constructs exhibited ability to differentiate MSCs into osteoblasts. MSCs responded best to micro−/nano‐structures created by final post‐processing by GB + AE, increasing OCN, OPG, VEGFA, latent TGFβ1, IL4, and IL10. Collectively these data demonstrate that M3D‐printed constructs can be readily manufactured with distinct architectures based on the print parameters and post‐build modifications. MSCs are sensitive to discrete surface topographical differences that may not show up in qualitative assessments of surface properties and respond by altering local factor production. These factors are vital for osseointegration after implant insertion, especially in patients with compromised bone qualities.
Allogeneic hematopoietic stem cell transplantation in non‐Hodgkin lymphoma in Switzerland, 30 years of experience: Sooner is better
Authors: Rebmann Ekaterina , Nabergoj Mitja , Grandjean Bastien , Stakia Paraskevi , Stern Alix , Medinger Michael , Masouridi‐Levrat Stavroula , Dantin Carole , Schanz Urs , Baldomero Helen , Passweg Jakob , Nair Gayathri , Rovo Alicia , Chalandon Yves
Published: November 2022

Due to relatively high nonrelapse mortality (NRM), allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in non‐Hodgkin's lymphoma (NHL) remains the ultimate line of treatment but the only curable approach in a setting of relapse/refractory disease. Here, we conducted a retrospective, multicenter, registry‐based analysis on patients who underwent allo‐HSCT for NHL in Switzerland, over 30‐year (1985–2020) period. The study included 301 allo‐HSCTs performed for NHL patients in three University Hospitals of Switzerland (Zurich, Basel and Geneva) 09/1985 to 05/2020. We assessed in univariate and multivariable analysis the impact on survivals (overall survival [OS], relapse free survival [RFS], relapse incidence [RI], and non‐treatment related mortality [NRM]). The maximum follow‐up was 25 years with median follow‐up for alive patients of 61 months. The median age at allo‐HSCT was 51 years. Three‐ and ‐year OS was ‐ 59.5% and 55.4%; 3‐ and 5‐year PFS was 50% and 44%; 3‐ and 5‐year NRM was 21.7% and 23.6%. RI at 3 and 5 years was 27.4% and 34.9%. In conclusion, our analysis of the entire Swiss experience of allo‐HSCT in patients with NHL shows promising 5‐ and possibly 10‐year OS and relatively acceptable NRM rates for such population, the majority being not in complete remission (CR) at the time of transplantation.
Diffusion‐Weighted Imaging of the Abdomen: Correction for Gradient Nonlinearity Bias in Apparent Diffusion Coefficient
Authors: Wang Jian , Ma Chao , Yang Panpan , Wang Zhen , Chen Yufei , Bian Yun , Shao Chengwei , Lu Jianping
Published: November 2022

Background

Gradient nonlinearity (GNL) introduces spatial nonuniformity bias in apparent diffusion coefficient (ADC) measurements, especially at large offsets from the magnet isocenter.

Purpose

To investigate the effects of GNL in abdominal ADC measurements and to develop an ADC bias correction procedure.

Study Type

Retrospective.

Phantom/Population

Two homemade ultrapure water phantoms/25 patients with histologically confirmed pancreatic ductal adenocarcinoma (PDAC).

Field Strength/Sequence

A 3.0 T/diffusion‐weighted imaging (DWI) with single‐shot echo‐planar imaging sequence.

Assessment

ADC bias was computed in the three orthogonal directions at different offset locations. The spatial‐dependent correctors of ADC bias were generated from the ADCs of phantom 1. The ADCs were estimated before and after corrections for the phantom 1 with both the proposed approach and the theoretical GNL correction method. For the patients, ADCs were measured in abdominal tissues including left and right liver lobes, PDAC, spleen, bilateral kidneys, and bilateral paraspinal muscles.

Statistical Test

Friedman tests and Wilcoxon tests.

Results

The ADC bias measured by phantom 1 was 9.7% and 12.6% higher in the right–left and anterior–posterior directions and 9.2% lower in the superior–inferior direction at the 150 mm offsets from the magnetic isocenter. The corrected vs. the uncorrected ADCs measurements (median: 2.20 × 10−3 mm2/sec for both the proposed method and the theoretical GNL method vs. 2.31 × 10−3 mm2/sec, respectively) and their relative ADC errors (0.014, 0.016, and 0.054, respectively) were lower in the phantom 1. The relative ADC errors substantially decreased after correction in the phantom 2 (median: 0.048 and −0.008, respectively). The ADCs of all the abdominal tissues were lower after correction except for the left liver lobes (P = 0.13).

Data Conclusion

GNL bias in abdominal ADC can be measured by a DWI phantom. The proposed correction procedure was successfully applied for the bias correction in abdominal ADC.

Evidence Level

3.

Technical Efficacy

Stage 1.
Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies
Authors: Rabaan Ali A. , Abas Abdul Hawil , Tallei Trina Ekawati , Al‐Zaher Mona A. , Al‐Sheef Noor M. , Fatimawali  , Al‐Nass Esraa Z. , Al‐Ebrahim Eba A. , Effendi Yunus , Idroes Rinaldi , Alhabib Mather F. , Al‐Fheid Hussain A. , Adam Ahmad Akroman , Bin Emran Talha
Published: November 2022

Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu‐like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future.
Approaching COVID‐19 with epidemiological genomic surveillance and the sustainability of biodiversity informatics in Africa
Authors: Aborode Abdullahi Tunde , Huang Helen , Wireko Andrew Awuah , Mehta Aashna , Kalmanovich Jacob , Abdul‐Rahman Toufik , Sikora Vladyslav , Awaji Aeshah A.
Published: November 2022

COVID‐19 is an acute respiratory illness caused by Severe Acute Respiratory Syndrome‐Coronavirus 2 (SARS‐CoV‐2). The first case was reported in Africa on February 14, 2020 and has surged to 11 million as of July 2022, with 43% and 30% of cases in Southern and Northern Africa. Current epidemiological data demonstrate heterogeneity in transmission and patient outcomes in Africa. However, the burden of infectious diseases such as malaria creates a significant burden on public health resources that are dedicated to COVID‐19 surveillance, testing, and vaccination access. Several control measures, such as the SHEF2 model, encompassed Africa's most effective preventive measure. With the help of international collaborations and partnerships, Africa's pandemic preparedness employs effective risk‐management strategies to monitor patients at home and build the financial capacity and human resources needed to combat COVID‐19 transmission. However, the lack of safe sanitation and inaccessible drinking water, coupled with the financial consequences of lockdowns, makes it challenging to prevent the transmission and contraction of COVID‐19. The overwhelming burden on contact tracers due to an already strained healthcare system will hurt epidemiological tracing and swift counter‐measures. With the rise in variants, African countries must adopt genomic surveillance and prioritize funding for biodiversity informatics.
Determination of skarn garnet compositions using Raman spectroscopy
Authors: Zhu Qiaoqiao , Cook Nigel J. , Xie Guiqing , Ciobanu Cristiana L. , Ji Yunhao
Published: November 2022

Garnet is a key and defining mineral of skarns and associated metalliferous deposits. Variation in garnet composition, commonly expressed by the proportions of different end‐members, is widely used to determine the physical–chemical features of hydrothermal fluids. Skarn garnets from the Fujiashan W‐Cu‐Mo deposit, eastern China, were investigated by Raman spectroscopy and electron probe microanalysis to assess the quantitative correlation between Raman band positions and proportions of garnet end‐members. Compositions and Raman band positions of so‐called “grandite” garnet (Adr18–98Grs0–79), where Adr and Gr are the end‐members andradite and grossular, respectively, display a spatial zonation at Fujiashan that correlates with the distance from the contact between skarn and causative intrusion. Raman band positions determined in the ranges 234–246, 351–368, 369–375, 515–544, 814–826, and 873–882 cm−1 demonstrate moderate to very strong (R2 up to 0.99) linear correlations with mol% andradite and grossular components. This is attributed to homovalent substitution between Fe3+ and Al3+ in the octahedral site, which has an indirect effect on bond lengths and angles of Si‐O vibration, resulting in linear variation of Raman band positions. The band between 515 and 544 cm−1 is the most sensitive to compositional variation, and its position enables robust estimation of end‐member proportions within 10% of results calculated from electron probe microanalysis. This research highlights the potential of Raman spectroscopy as a rapid, powerful method to assess the composition of skarn garnet, enabling accelerated construction of spatial zonation models for skarns during skarn deposit exploration.
A novel method for quality consistency evaluation of Glycyrrhiza formula granules based on a spectrum‐effect study
Authors: Zhou Yongfeng , Wang Junnan , Tan Peng , Wu Qinghua , Chen Jiang , Liu Jiaxin , Zhang Ping , Zhang Dingkun , Pei Jin
Published: November 2022

Quality consistency of Glycyrrhiza formula granules is essential for guaranteeing clinical efficacy. However, a suitable method to accurately and conveniently evaluate the consistency of the clinical efficacy of Glycyrrhiza formula granules is currently not available. This study established a method for the simultaneous determination of 12 active components in Glycyrrhiza formula granules using ultra‐high‐performance liquid chromatography coupled with quadrupole‐time‐of‐flight tandem mass spectrometry. The rate of inhibition of cyclooxygenase‐2 by different batches of Glycyrrhiza formula granules was determined. Near‐infrared spectra were collected for different batches of Glycyrrhiza formula granules to detect their biological activity in the inhibition of cyclooxygenase‐2. The quality consistency of the 11 batches of Glycyrrhiza formula granules was evaluated using principal component and correlation analyses. The results showed significant differences in the formula granules of Glycyrrhiza uralensis produced by the different manufacturers. Some differences were also observed among batches of formula granules produced by the same manufacturer. Correlation analysis of the chemical components and cyclooxygenase‐2 activity showed that glycyrrhizic acid, liquiritin, and isoliquiritin were the main active components of Glycyrrhiza. Correlation analysis of the near‐infrared spectra and cyclooxygenase‐2 inhibition activity showed a high correlation between the active components and three characteristic bands: 3383–3995, 4227–4651, and 5315–5878 cm−1. In this study, the main active anti‐inflammatory components of Glycyrrhiza granules were screened. Thus, the near‐infrared spectrum and characteristic active band of multi‐index active components can be used to quickly detect the quality consistency of Glycyrrhiza formula granules, thereby improving the ability to control the quality and consistency of these granules.
A newborn male with Myhre syndrome, hearing loss, and complete syndactyly of fingers 3–4
Authors: Yang Kun , Wang Xi , Wang Wei‐Qian , Han Ming‐Yu , Hu Li‐Min , Kang Dong‐Yang , Yang Jin‐Yuan , Liu Min , Gao Xue , Yuan Yong‐Yi , Xu Jin‐Cao
Published: November 2022

Background

Myhre syndrome is a rare multisystem genetic disorder that is caused by de novo heterozygous gain‐of‐function variants in SMAD4. Patients with Myhre syndrome exhibit several phenotypes at different ages such as small size, autism, developmental delay, left‐sided heart defects, and hearing loss and often have a characteristic facial appearance. The early clinical diagnosis of Myhre syndrome remains a major challenge, particularly in the first year of life.

Methods

A Chinese male infant with syndactyly of fingers, hypertelorism, short palpebral fissures, and short philtrum was enrolled into the ENT department of the Chinese PLA General Hospital. Whole exome sequencing analysis was used to detect the disease‐causing variant. A literature review of Myhre syndrome was also performed.

Results

A recurrent de novo missense variant c.1498A > G p.I500V(p. Ile500Val) in SMAD4 was detected confirming the clinical diagnosis of Myhre syndrome at the age of 38 days. The infant appears to be the youngest reported case of Myhre syndrome. At 23‐month follow‐up, the affected infant has dysmorphic facial features, growth retardation, and previously undescribed complete syndactyly. Review the literatures noted several common features in Myhre syndrome patients including hearing loss (72.7%), characteristic facial features (26.0%–54.5%), finger and toe abnormalities (3.9%–48.1%), short stature (45.5%), and respiratory (30.0%) and cardiovascular problems (65.0%).

Conclusions

Clinicians should have a low threshold to perform genetic testing on patients with features suggesting Myhre syndrome even in the first year of life. Although some individuals with Myhre syndrome have normal hearing, early onset or progressive hearing loss usually occur in one or both ears in most patients, with remarkable phenotypic heterogeneity. Syndactyly may be minor such as typical 2–3 toe involvement, or more complicated as was observed in our patient.
Ultrafast Z‐spectroscopic imaging in vivo at 3T using through‐slice spectral encoding (TS‐UFZ)
Authors: Bie Chongxue , van Zijl Peter C. M. , Mao Deng , Yadav Nirbhay N.
Published: November 2022

Purpose

Acquisition of high‐resolution Z‐spectra for CEST or magnetization transfer contrast (MTC) MRI requires excessive scan times. Ultrafast Z‐spectroscopy (UFZ) has been proposed to address this; however, the quality of in vivo UFZ spectra has been insufficient. Here, we present a simple approach to improve this.

Theory and Methods

UFZ imaging acquires full Z‐spectra by encoding the spectral dimension spatially via a gradient applied concurrently with the RF saturation pulse. Different from previous implementations, both this saturation gradient and its readout were applied in the slice direction, resulting in a relatively uniform voxel composition. Phase‐encoding was applied in both in‐plane directions, allowing additional under‐sampling and acceleration.

Results

In phantoms, UFZ imaging with through‐slice Z‐spectral encoding (TS‐UFZ) provided Z‐spectra of salicylic acid and egg white in excellent agreement with conventional acquisitions. In vivo brain Z‐spectra were influenced by flow through the imaging slice which affected the Z‐spectral baseline. Still, CEST signals could be quantified after baseline fitting and mapping the residual CEST signal. Amide proton transfer (APT) contrast intensities obtained by TS‐UFZ were on the same order of magnitude as conventional CEST but with different contrast across slice which likely is a result of different tissue regions contributing.

Conclusion

TS‐UFZ approach improves signal stability and spectral uniformity over previous implementations and allows high spectral‐resolution imaging of saturation transfer effects in the human brain at 3T. This implementation allows for further acceleration by reducing phase encoding steps and thus opens up the possibility of mapping dynamic CEST signals in vivo with a practical temporal resolution.