bluuebunny/crossref_metadata_2025 huggingface dataset:
The discordant biomarker dilemma: What are the diagnostic implications of oropharyngeal squamous cell carcinomas with discrepant p16 and HPV results?
Authors: Guzmán‐Arocho Yaileen D. , Nishino Michiya
Published: June 2022

Discordant p16 and human papillomavirus (HPV)‐specific testing results, although uncommon in oropharyngeal squamous cell carcinomas, present a quandary to pathologists and treating clinicians alike. This commentary outlines potential scenarios leading to p16/HPV discordance and highlights recent studies that shed some light on the prognostic significance thereof.
Physiologically‐Based Pharmacokinetic Modeling‐Guided Dose Management of Oral Anticoagulants when Initiating Nirmatrelvir/Ritonavir (Paxlovid) for COVID‐19 Treatment
Authors: Wang Ziteng , Chan Eric Chun Yong
Published: June 2022

Patients with coronavirus disease 2019 (COVID‐19) with cardiovascular diseases who are at higher risk of progressing to critical illness should be treated with nirmatrelvir/ritonavir (Paxlovid). Ritonavir, the booster in nirmatrelvir/ritonavir, modulates multiple drug metabolizing enzymes and transporters, complicating its use in real‐world clinics. We aimed to apply physiologically‐based pharmacokinetic (PBPK) modeling to simulate the complex drug–drug interactions (DDIs) of ritonavir with two anticoagulants, rivaroxaban and racemic warfarin, to address this important clinical conundrum. Simulations were implemented within Simcyp Simulator. Compound and population models were adopted from Simcyp and our previous studies. Upon verification and validation of the PBPK model of ritonavir, prospective DDI simulations with the anticoagulants were performed in both the general population (20–65 years) and geriatric subjects (65–85 years) with or without moderate renal impairment. Elevated rivaroxaban concentrations were simulated with nirmatrelvir/ritonavir treatment, where the impact was more profound among geriatric subjects with renal impairment. The overexposure of rivaroxaban was restored to normal range on day 4 post‐discontinuation of nirmatrelvir/ritonavir, corroborating with the recovery of enzyme activity. A lower 10 mg daily dose of rivaroxaban could effectively maintain acceptable systemic exposure of rivaroxaban during nirmatrelvir/ritonavir treatment. Treatment of ritonavir marginally declined simulated S‐warfarin concentrations, but substantially elevated that of R‐warfarin, resulting in a decrease in the international normalized ratio (INR). As INR only recovered 2 weeks post‐nirmatrelvir/ritonavir treatment, a longer surveillance INR for warfarin becomes important. Our PBPK‐guided simulations evaluated clinically important yet untested DDIs and supports clinical studies to ensure proper anticoagulation management of patients with COVID‐19 with chronic coagulative abnormalities when initiating nirmatrelvir/ritonavir therapy.
White Light Generating Molecular Materials: Correlation Between the Amorphous/Crystalline Structure and Nonlinear Optical Properties
Authors: Haust Johannes , Belz Jürgen , Müller Marius , Danilo Klee Benjamin , Link Vasco Jonathan , Hüppe Franziska , Rojas Léon Irán , Christmann Jan , Beyer Andreas , Dehnen Stefanie , Rosemann Nils W. , Pilgrim Wolf‐Christian , Chatterjee Sangam , Volz Kerstin
Published: June 2022

The front cover artwork is provided by Johannes Haust, Jürgen Belz, Kerstin Volz (Philipps‐University Marburg) and Sangam Chatterjee (Justus Liebig University Giessen). The image illustrates the generation of a transmission electron microscopy diffraction pattern from the amorphous adamantane‐type cluster compound [(PhSn)4S6] (Ph=phenyl) as well as the conversion of red light from a continuous wave infrared laser into directed white light when propagating through the sample. Cover design by Elisa Monte. Read the full text of the Research Article at 10.1002/cptc.202200071.
Production and Purification of Shark and Camel Single‐Domain Antibodies from Bacterial and Mammalian Cell Expression Systems
Authors: Duan Zhijian , Buffington Jesse , Hong Jessica , Ho Mitchell
Published: June 2022

Single‐domain antibodies, including the antigen‐binding variable domains of the shark immunoglobulin new antigen receptor and the camelid variable region of the heavy chain, are the smallest antigen recognition domains (∼15 kDa) and have unique characteristics compared to conventional antibodies. They are capable of binding epitopes that are hard to access for classical antibodies and can also be used for therapeutics or diagnostics or as modular building blocks for multi‐domain constructs, antibody‐drug conjugates, immunotoxins, or chimeric antigen receptor therapy. This article contains detailed procedures for the purification and validation of two single‐domain antibodies (one shark and one camel), which bind to the S2 subunit of the SARS‐CoV‐2 spike protein, using both bacterial and mammalian cell expression systems. It provides a comprehensive reference for the production of single‐domain antibodies with high yield, good quality, and purity. © Published 2022. This article is a U.S. Government work and is in the public domain in the USA.

Basic Protocol: Production of single‐domain antibodies from Escherichia coli

Alternate Protocol: Production of single‐domain antibodies using the mammalian cell line Expi293F

Support Protocol 1: Production and purification of single‐domain antibodies on a small scale with the polymyxin B method

Support Protocol 2: Validation of single‐domain antibodies by ELISA
Oral hygiene knowledge versus behavior in children: A questionnaire‐based, interview‐style analysis and on‐site assessment of toothbrushing practices
Authors: Gund Madline P. , Bucher Marina , Hannig Matthias , Rohrer Tilman R. , Rupf Stefan
Published: June 2022

Objectives

Oral hygiene plays an important role in eliminating biofilms and preventing dental caries. However, the implementation of oral health knowledge that children learn from their parents and through school dental health programmes remains poorly studied. This study aimed to investigate oral hygiene knowledge and its practical utilization in children and young adolescents (CYAs) aged 2–15 years.

Material and methods

This was a questionnaire‐based, interview‐style community survey and on‐site practical assessment of CYAs' toothbrushing skills conducted during two 1‐day public science‐promoting events held at a major German university hospital in consecutive years. CYAs first answered questions on toothbrushing frequency, dental aids used, and dental care. They subsequently underwent diagnostic staining and demonstrated their brushing technique and method. CYAs' responses (percentages) to questionnaire items addressing oral hygiene knowledge and practice, and on‐site assessment of toothbrushing skills served as the main outcome measures.

Results

Of 244 participating CYAs, 178 (73%) CYAs had no caries experience, the percentage increasing with age from 5% in 2–5‐year‐olds to 40% in those aged > 10 years. Of 117/244 (48%) indicating that teeth should be brushed three times daily, 80/117 (68%) self‐reported twice‐daily brushing, 32/117 (27%) reported brushing three times, and 4/117 (3%) stated doing so only once. Although 131/244 (54%) considered that teeth should be brushed for 3 min, 77/131 (59%) self‐reported actually doing so and 41/131 (31%) reported brushing for 2min. Seventeen of 42 (40%) participants aged > 10 years showed no systematic brushing method, with 21/42 (50%) failing to clean their teeth completely. Participants aged 6–10 years exhibited the highest proportion (97/134, 72%) of complete cleaning. One hundred and forty‐six of 244 (60%) of CYAs knew about floss; 63/134 (43%) reported using it. Good adherence to oral health recommendations (i.e., brushing ≥ 2/day for ≥2min) was observed in 212/244 (87%) CYAs, the remaining 32/244 (13%) exhibiting poor adherence.

Conclusion

CYAs knew about the importance of oral hygiene and cleaned their teeth frequently. However, translation of their knowledge into practice showed deficiencies. Repeated encouragement to put oral health knowledge into practice is important.
Core–shell NaBH4@Ni Nanoarchitectures: A Platform for Tunable Hydrogen Storage
Authors: Salman Muhammad Saad , Yang Yuwei , Zubair Muhammad , Bedford Nicholas M. , Aguey‐Zinsou Kondo‐Francois
Published: June 2022

The core–shell approach has surfaced as an attractive strategy to make complex hydrides reversible for hydrogen storage; however, no synthetic method exists for taking advantage of this approach. Here, a detailed investigation was undertaken to effectively design freestanding core–shell NaBH4@Ni nanoarchitectures and correlate their hydrogen properties with structure and chemical composition. It was shown that the Ni shell growth on the surface of NaBH4 particles could be kinetically and thermodynamically controlled. The latter led to varied hydrogen properties. Near‐edge X‐ray absorption fine structure analysis confirmed that control over the Ni0/NixBy concentrations upon NiII reduction led to a destabilized hydride system. Hydrogen release from the sphere, cube, and bar‐like core–shell nanoarchitectures occurred at around 50, 90, and 95 °C, respectively, compared to the bulk (>500 °C). This core–shell approach, when extended to other hydrides, could open new avenues to decipher structure–property correlation in hydrogen storage/generation.
Hydrophilic Crosslinked TEMPO‐Methacrylate Copolymers – a Straight Forward Approach towards Aqueous Semi‐Organic Batteries
Authors: Elbinger Lada , Schröter Erik , Friebe Christian , Hager Martin D. , Schubert Ulrich S.
Published: June 2022

Crosslinked hydrophilic poly(2,2,6,6‐tetramethylpiperidinyl‐N‐oxyl‐co‐[2‐(methacryloyloxy)‐ethyl]trimethyl ammonium chloride) [poly(TEMPO‐co‐METAC)] polymers with different monomer ratios are synthesized and characterized regarding a utilization as electrode material in organic batteries. These polymers can be synthesized rapidly utilizing commercial starting materials and reveal an increased hydrophilicity compared to the state‐of‐the‐art poly(2,2,6,6‐tetramethylpiperidinyl‐N‐oxyl‐4‐methacrylate) (PTMA). By increasing the hydrophilicity of the polymer, a preparation of cathode composites is enabled, which can be used for aqueous semi‐organic batteries. Detailed battery testing confirms that the additional METAC groups do not impair the battery behavior while enabling straight‐forward zinc‐TEMPO batteries.
Community assembly, functional traits, and phylogeny in Himalayan river birds
Authors: Sinha Ankita , Chatterjee Nilanjan , Krishnamurthy Ramesh , Ormerod Steve J.
Published: June 2022

Heterogeneity in riverine habitats acts as a template for species evolution that influences river communities at different spatio‐temporal scales. Although birds are conspicuous elements of these communities, the roles of phylogeny, functional traits, and habitat character in their niche use or species' assembly have seldom been investigated. We explored these themes by surveying multiple headwaters over 3000 m of elevation in the Himalayan Mountains of India where the specialist birds of montane rivers reach their greatest diversity on Earth. After ordinating community composition, species traits, and habitat character, we investigated whether river bird traits varied with elevation in ways that were constrained or independent of phylogeny, hypothesizing that trait patterns reflect environmental filtering. Community composition and trait representation varied strongly with increasing elevation and river naturalness as species that foraged in the river/riparian ecotone gave way to small insectivores with direct trophic dependence on the river or its immediate channel. These trends were influenced strongly by phylogeny as communities became more clustered by functional traits at a higher elevation. Phylogenetic signals varied among traits, however, and were reflected in body mass, bill size, and tarsus length more than in body size, tail length, and breeding strategy. These variations imply that community assembly in high‐altitude river birds reflects a blend of phylogenetic constraint and habitat filtering coupled with some proximate niche‐based moulding of trait character. We suggest that the regional co‐existence of river birds in the Himalaya is facilitated by this same array of factors that together reflect the highly heterogeneous template of river habitats provided by these mountain headwaters.
Atrial fibrillation is an independent risk factor for heart failure hospitalization in heart failure with preserved ejection fraction
Authors: Yang Eunice , Vaishnav Joban , Song Evelyn , Lee Joan , Schulman Steven , Calkins Hugh , Berger Ronald , Russell Stuart D. , Sharma Kavita
Published: June 2022

Aims

Atrial fibrillation (AF) is a common comorbid condition in heart failure with preserved ejection fraction (HFpEF). The effect of AF on heart failure (HF) exacerbation in HFpEF has not been well described. This study investigated how AF modifies the clinical trajectory of HFpEF patients after hospitalization for decompensated HF.

Methods and results

We stratified HFpEF subjects by AF diagnosis and performed longitudinal analysis to compare risk for HF hospitalization after index hospitalization for decompensated HF. All‐cause mortality, 30 day all‐cause readmissions, and response to inpatient diuresis were also evaluated. Of 90 subjects enrolled, 35.6% (n = 32) had AF. Subjects with AF were older (72.5 vs. 60.5 years; P < 0.01), more often male (46.9% vs. 24.1%; P = 0.03), and had greater left atrial diameter (4.9 vs. 3.8 cm; P < 0.01) compared with those without AF. Subjects with AF had a higher risk for HF hospitalization than their counterparts without AF (P = 0.02); this relationship remained significant following multivariable competing risk regression with propensity score weighting (hazard ratio 2.53, P = 0.04 and hazard ratio 2.91, P = 0.04, with overlap and inverse probability weighting, respectively). Although having AF appeared to increase the risk of all‐cause hospital readmission within 30 days of discharge (37.5% vs. 17.5%; P = 0.036), this relationship failed to remain significant following propensity score adjustment for clinical covariates.

Conclusions

Atrial fibrillation is an independent risk factor for HF rehospitalization in HFpEF. Further understanding of the interplay between AF and HFpEF will be critical to guide the selection of appropriate rhythm management strategies in this population.
Angiotensin receptor‐neprilysin inhibitor in symptomatic patients with Duchenne dilated cardiomyopathy: A primetime
Authors: Arcudi Alessandra , Di Francesco Marco , Rodolico Daniele , D'Amario Domenico
Published: June 2022

Aims

Duchenne muscular dystrophy (DMD) is an X‐linked recessive neuromuscular disorder, characterized by significant long‐term cardiac involvement. Dilated cardiomyopathy (DCM) is the main cause of death in DMD, and angiotensin‐converting enzyme inhibitors (ACEi) and beta‐blockers (BB) are first‐line treatments in DCM. It is unknown whether angiotensin receptor‐neprilysin inhibitor (ARNi) could provide greater benefits in this setting. Our aim is to assess whether ARNi use may prevent deterioration in ejection fraction (EF) or is associated with EF improvement compared with ACEi in DMD patients with heart failure and to report the tolerability of ARNi in this group of patients.

Methods and results

We followed 22 DMD patients, 6 of them with an EF < 40% and 16 with an EF > 40%. The first group received ARNi on top of BB, while the control group started or continued first‐line therapy with ACEi ± BB. From December 2016 to December 2021, we recorded EF values at baseline and at follow‐up, comparing EF changes. Median follow‐up was 7 months (interquartile range 4.7–9.1). At baseline, the mean of EF (%) in the ARNi group was 31 ± 2%, while it was 59 ± 9% in the control group. At follow‐up, we recorded an EF improvement in the ARNi group (38 ± 6%, P‐value < 0.05). Among controls, EF at follow‐up was substantially unchanged from baseline.

Conclusions

Our data suggest that the use of ARNi in DMD patients with DCM and an EF < 40% might be associated with an EF improvement and a safe tolerability profile.
Diversity‐Oriented Synthesis and Chemoinformatics: A Fruitful Synergy towards Better Chemical Libraries
Authors: Lenci Elena , Trabocchi Andrea
Published: June 2022

In these two decades, Diversity‐Oriented Synthesis (DOS) has changed significantly: from the historical focus on structural diversity, new approaches have been developed in order to increase the biological outcome of the molecules within the library, such as the privileged‐based DOS or the Diversity‐Oriented Fluorescence Library Approach (DOFLA). In this context, chemoinformatics can assist organic chemists in identifying biologically‐relevant regions of the chemical space not yet explored. Also, chemoinformatics tools can be used to graphically visualize and/or predict the structural diversity and complexity of the compounds within the library. This review highlights the improvement that DOS has received from chemoinformatics, presenting recent articles (published between 2016 and 2021) in which DOS libraries are analysed by chemoinformatics tools.
Gyral peaks: Novel gyral landmarks in developing macaque brains
Authors: Zhang Songyao , Chavoshnejad Poorya , Li Xiao , Guo Lei , Jiang Xi , Han Junwei , Wang Li , Li Gang , Wang Xianqiao , Liu Tianming , Razavi Mir Jalil , Zhang Shu , Zhang Tuo
Published: June 2022

Cerebral cortex development undergoes a variety of processes, which provide valuable information for the study of the developmental mechanism of cortical folding as well as its relationship to brain structural architectures and brain functions. Despite the variability in the anatomy–function relationship on the higher‐order cortex, recent studies have succeeded in identifying typical cortical landmarks, such as sulcal pits, that bestow specific functional and cognitive patterns and remain invariant across subjects and ages with their invariance being related to a gene‐mediated proto‐map. Inspired by the success of these studies, we aim in this study at defining and identifying novel cortical landmarks, termed gyral peaks, which are the local highest foci on gyri. By analyzing data from 156 MRI scans of 32 macaque monkeys with the age spanned from 0 to 36 months, we identified 39 and 37 gyral peaks on the left and right hemispheres, respectively. Our investigation suggests that these gyral peaks are spatially consistent across individuals and relatively stable within the age range of this dataset. Moreover, compared with other gyri, gyral peaks have a thicker cortex, higher mean curvature, more pronounced hub‐like features in structural connective networks, and are closer to the borders of structural connectivity‐based cortical parcellations. The spatial distribution of gyral peaks was shown to correlate with that of other cortical landmarks, including sulcal pits. These results provide insights into the spatial arrangement and temporal development of gyral peaks as well as their relation to brain structure and function.
Eosinophils protect against acetaminophen‐induced liver injury through cyclooxygenase‐mediated IL‐4/IL‐13 production
Authors: Xu Long , Yang Yang , Jiang Jiali , Wen Yankai , Jeong Jong‐Min , Emontzpohl Christoph , Atkins Constance L. , Kim Kangho , Jacobsen Elizabeth A. , Wang Hua , Ju Cynthia
Published: June 2022

Background and Aims:

A better understanding of the underlying mechanism of acetaminophen (APAP)‐induced liver injury (AILI) remains an important endeavor to develop therapeutic approaches. Eosinophils have been detected in liver biopsies of patients with APAP overdose. We recently demonstrated a profound protective role of eosinophils against AILI; however, the molecular mechanism had not been elucidated.

Approach and Results:

In agreement with our previous data from experiments using genetic deletion of eosinophils, we found that depletion of eosinophils in wild‐type (WT) mice by an anti‐IL‐15 antibody resulted in exacerbated AILI. Moreover, adoptive transfer of eosinophils significantly reduced liver injury and mortality rate in WT mice. Mechanistic studies using eosinophil‐specific IL‐4/IL‐13 knockout mice demonstrated that these cytokines, through inhibiting interferon‐γ, mediated the hepatoprotective function of eosinophils. Reverse phase protein array analyses and in vitro experiments using various inhibitors demonstrated that IL‐33 stimulation of eosinophils activated p38 mitogen‐activated protein kinase (MAPK), and in turn, cyclooxygenases (COX), which triggered NF‐κB–mediated IL‐4/IL‐13 production. In vivo adoptive transfer experiments showed that in contrast to naive eosinophils, those pretreated with COX inhibitors failed to attenuate AILI.

Conclusions:

The current study revealed that eosinophil‐derived IL‐4/IL‐13 accounted for the hepatoprotective effect of eosinophils during AILI. The data demonstrated that the p38 MAPK/COX/NF‐κB signaling cascade played a critical role in inducing IL‐4/IL‐13 production by eosinophils in response to IL‐33.
Embedding experiential learning in undergraduate health promotion curriculum
Authors: Chong Susan C. S. , Anderson Karen , Mackenzie‐Stewart Ruth , Hobbs Carmel , Conna Belinda
Published: June 2022

Issue addressed

The experiential teaching method draws on research‐based principles of adult education. The integration of academic learning and practice provides students opportunities to increase their knowledge while developing capabilities to meet the International Union for Health Promotion and Education (IUHPE) Core Competencies and Professional Standards.

Methods

Community Health Promotion is a second‐year subject offered in the Bachelor of Health Sciences at La Trobe University. The project‐based curriculum, delivered over 12 weeks, consists of theoretical material which students apply through hands‐on project planning, implementation and evaluation; projects are carried out on campus. To bridge academic content and project practicalities the Victorian government's Integrated Health Promotion Resource Kit is used as a foundational teaching resource. Students are supported by teaching staff and a project sponsor throughout the project cycle. Assessment tasks comprised of problem definition and priority setting, project planning and critical reflection on project implementation.

Discussion

The experiential learning approach enables students, in a self‐directed yet collaborative manner, to develop skills aligned with health promotion competencies. Students were able to safely “experiment” and apply health promotion theory while actively developing project management and partnerships skills, reflecting on their practice and communicating project findings. Students consistently provide feedback articulating the value they place on the purposeful and scaffolded transition of classroom learning to real‐life environments which they recognised as building their competencies and enhancing their employability skills.

Conclusion

Experiential learning through small‐group projects prepares students for the health promotion workforce in a low‐risk, high‐impact educational setting while contributing to promoting the ethos of a health‐promoting university.

So what?

The authentic assessments provide students with the opportunity to develop competency within several domains of the IUHPE Core Competencies and Professional Standards.
Waka ama: An exemplar of indigenous health promotion in Aotearoa New Zealand
Authors: Reweti Angelique , Severinsen Christina
Published: June 2022

Issue addressed

The use of old‐style, top‐down health education and awareness programmes in Aotearoa New Zealand, which adopt a single issue‐based approach to health promotion, primarily ignores a broad approach to social determinants of health, as well as indigenous Māori understandings of wellbeing.

Methods

This paper draws on the indigenous framework Te Pae Māhutonga as a guide for presenting narratives collated from members of a waka ama rōpū (group) who were interviewed about the social, cultural and health benefits of waka ama.

Results

This waka ama case study is an exemplar of community‐led health promotion within an indigenous context, where Māori values and practices, such as whanaungatanga (the process of forming and maintaining relationships), manaakitanga (generosity and caring for others) and kaitiakitanga (guardianship), are foundational. The findings highlight the multiple benefits of engagement in waka ama and illustrate effective techniques for enhancing wellbeing within local communities.

Conclusion

At a time when Aotearoa New Zealand is seeing a decreasing trend in physical activity levels and an increase in mental health challenges, waka ama provides us with an exemplar of ways to increase health and wellbeing within our communities.

So what?

The findings of this research contribute to the evidence base of effective indigenous health promotion, bridging the gap between academia and local community action. To better recognise, comprehend and improve indigenous health and wellbeing, we argue that active participation of people in the community is required to achieve long‐term and revolutionary change.
The promising novel therapies for familial hypercholesterolemia
Authors: Chen Ruoyu , Lin Shaoyi , Chen Xiaomin
Published: June 2022

Background

The incidence of premature atherosclerotic cardiovascular disease in familial hypercholesterolemia (FH) is high. In recent years, novel therapeutic modalities have shown significant lipid‐lowering ability. In this paper, we summarize the recent developments in novel therapies for FH via the treatment of different targets and discuss the characteristics of each targeted therapy. Based on the process of protein synthesis, we attempt to summarize the direct‐effect targets including protein, RNA, and DNA.

Methods

For this systematic review, relevant studies are assessed by searching in several databases including PubMed, Web of Science, Scopus, and Google Scholar. The publications of original researches are considered for screening.

Results

Most drugs are protein‐targeted such as molecule‐based and monoclonal antibodies, including statins, ezetimibe, alirocumab, evolocumab, and evinacumab. Both antisense oligonucleotide (ASO) and small interfering RNA (siRNA) approaches, such as mipomersen, vupanorsen, inclisiran, and ARO‐ANG3, are designed to reduce the number of mRNA transcripts and then degrade proteins. DNA‐targeted therapies such as adeno‐associated virus or CRISPR–Cas9 modification could be used to deliver or edit genes to address a genetic deficiency and improve the related phenotype.

Conclusion

While the therapies based on different targets including protein, RNA, and DNA are on different stages of development, the mechanisms of these novel therapies may provide new ideas for precision medicine.
Pregnancy in cystinosis patients with chronic kidney disease: A European case series
Authors: Servais Aude , Janssen Mirian C. H. , Blakey Hannah , Greco Marcella , Lemoine Sandrine , Martin‐Moreno Paloma L. , Game David , Levtchenko Elena , Lipkin Graham ,   Metabolic Nephropathy Workgroup of the European Reference Network for Rare Kidney Diseases (ERKNet) and the ERA working groups on inherited kidney diseases (WGIKD)
Published: June 2022

Cystinosis is a rare autosomal recessive disease leading to end‐stage renal disease within the second or third decade of life. Since the era of specific treatment with cysteamine, prognosis has substantially improved and pregnancy becomes an increasing concern. Pregnancy data in patients with cystinosis were collected through an anonymized survey. We collected data for 19 pregnancies in 12 women. Seventeen patients were transplanted, 1 was on hemodialysis and 1 had chronic kidney disease (CKD) stage 4. These 19 pregnancies resulted in 13 live births (68.4%): 3 spontaneous early miscarriages, 1 ectopic pregnancy, 1 early pre‐eclampsia (at 21 weeks), and 1 preterm birth with neonatal death at 24 weeks were reported. After exclusion of early miscarriage or termination, pregnancy success rate was 86.7%. In successful pregnancies, median gestational age at delivery was 34 weeks (24–37). Preeclampsia occurred in seven pregnancies (7/15, 46.7%). A cesarean section was performed in all pregnancies. Median baby weight at delivery was 2175 g (620–3374 g). After pregnancy, one patient reached end‐stage renal disease, but she already had advanced CKD before pregnancy (creatinine 239 μmol/L, eGFR 23 ml/min/1.73 m2). In three other patients, there was a decrease of eGFR of 8, 20, and 53 ml/min/1.73 m2, respectively. The majority of pregnancies were successful, but severe antenatal and post‐natal complications may occur, in particular preeclampsia that was noticed in nearly half of patients and fetal loss in one‐third of them. These results may help pre‐pregnancy counseling and pregnancy management.
Suboptimal immune recovery and associated factors among people living with HIV/AIDS on second‐line antiretroviral therapy in central China: A retrospective cohort study
Authors: Zhu Keying , Xu Qianlei , Ma Yanmin , Li Pengyu , Jia Huangchao , Jiang Qi , Wang Yueyuan , Wu Zhihui , Wang Dongli , Guo Huijun , Jin Yantao
Published: June 2022

The introduction and scale‐up of antiretroviral therapy (ART) have contributed to significantly improved patients with acquired immune deficiency syndrome (AIDS) quality of life and prolongs their survival. This has occurred by suppressing viral replication and recovering the CD4 cell count. However, some patients do not normalize their CD4 cell count, despite suppression of the viral load (VL). Patients with suboptimal immune recovery (SIR), as defined by a VL < 400 copies/ml with a CD4 cell count of<200 cells/μl, after ART initiation, exhibit severe immune dysfunction and have a higher risk of AIDS and non‐AIDS events. In recent years, People living with HIV/AIDS (PLWHA) with first‐line ART failure began to gradually switch to second‐line ART. This study aimed to examine the prevalence and factors affecting SIR among PLWHA who switch to second‐line ART in rural China. A 1‐year retrospective cohort study was conducted among PLWHA who switched to second‐line ART between January 2009 and December 2018. All patients with a VL < 400 copies/ml after 1 year of second‐line ART were included. SIR was defined as a CD4 cell count <200 cells/μl and a VL < 400 copies/ml after 1 year of second‐line ART. The data collected from medical records were analyzed by univariate and multivariate analyses. A total of 5294 PLWHA met the inclusion criteria, 24 died, and 1152 were lost to follow‐up after 1 year of second‐line ART. Among 4118 PLWHA who were followed up, 3039 with a VL < 400 copies/ml had their data analyzed, and the prevalence of SIR was 13.1%. The patients’ mean age at recruitment was 47.6 ± 8.1 years and 45.3% were men. A total of 30.7% of patients were HIV‐positive for >8 years and 88.2% were receiving ART before starting second‐line ART for >3 years. The mean CD4 cell count was 354.8 ± 238.2 cells/μl. A multivariable analysis showed that male sex, single status (unmarried or divorced), and a low CD4 cell count were risk factors for SIR among PLWHA with second‐line ART. The prevalence of SIR among PLWHA who switched to second‐line ART in this retrospective cohort study is lower than that in most other studies. Several factors associated with SIR include male sex, marital status, and CD4 cell count levels in PLWHA.
Associations among bullous pemphigoid and various neurological diseases: A systematic review and meta‐analysis
Authors: Chen Qianqian , Wu Huangshuai , Lyu Yansi , Xiong Juan
Published: June 2022

Bullous pemphigoid is a common autoimmune bullous skin disease of the elderly. The objective of this meta‐analysis was to assess the association of bullous pemphigoid with neurological disease. We conducted a systematic search of three databases, screening for articles with relevant search terms from database inception until August 01, 2020. The Newcastle‐Ottawa quality assessment scale was used to evaluate the quality of the retained articles. Random effects models were applied to calculate the pooled odds ratio and confidence intervals. Publication bias was evaluated by funnel plot and Egger's test. A total of 25 studies with 44,726 BP patients were included in this meta‐analysis. Patients with BP were significantly more likely to have any neurological disease [odds ratio (OR): 4.5, 95% confidence interval (CI): 3.2–6.5]. This was true for: stroke (OR: 2.7, 95% CI: 2.2–3.4), Parkinson's disease (OR: 2.7, 95% CI: 2.2–3.2), dementia (OR: 4.1, 95% CI: 3.0–5.7), Alzheimer's disease (OR: 2.3, 95% CI: 1.2–4.4), epilepsy (OR: 2.4, 95% CI: 1.6–3.5), and multiple sclerosis (OR: 3.3, 95% CI: 2.1–5.2), compared to controls. Bullous pemphigoid patients have an increased prevalence of neurological disease. Clinicians should be aware of this increased prevalence, its possible implications, and preventive measures for patients.
Variation and protection of the chorda tympani nerve in endoscopic ear surgery
Authors: Quancheng Li , Jiangtao Zhong , Liang Chai
Published: June 2022

Objective

To observe and summarize variations of the chorda tympani nerve to effectively protect it during surgery.

Methods

Surgical videos of patients undergoing endoscopic ear surgery in the past 3 years were retrospectively observed to identify chorda tympani nerve variations.

Results

In total, 237 cases were reviewed. The tympanic sulcus or annulus was the boundary between the posterior wall of the external auditory canal and chordal eminence (CE). The chorda tympani nerve was divided into three types: type I, the periannular segment was located medial to the CE and covered by the bony eminence (32.5%); type II, the periannular segment was located inferior to the CE, and the nerve did or did not contact the bony edge of the CE (62.0%); and type III, the periannular segment was located lateral to the CE and medial to the tympanic annulus, and the iter chorda posterius was located in the tympanic sulcus (5.5%). The rate of injury to the chorda tympani nerve was 2.5% of 237 cases. The location of the iter chorda posterius on preoperative computed tomography was highly reliable for prediction of type I and III nerves. Secondary exposure of the posterior canaliculus might occur in patients with external auditory canal cholesteatoma, who were specifically included in this study.

Conclusion

CE‐based classification of the chorda tympani nerve can concisely describe variations of the chorda tympani nerve and provide guidance for neuroprotection during endoscopic ear surgery. Patients with external auditory canal cholesteatoma may have secondary exposure of the posterior canaliculus.

Level of Evidence

NA.
The Synthesis and Properties of a New Carrier for Paclitaxel and Doxorubicin Based on the Amphiphilic Copolymer of N‐vinyl‐2‐pyrrolidone and Acrylic Acid
Authors: Nechaeva Anna M. , Artyukhov Alexander A. , Luss Anna L. , Shtilman Mikhail I. , Svistunova Alina Yu. , Motyakin Mikhail V. , Levina Irina I. , Krivoborodov Efrem G. , Toropygin Ilya Yu. , Chistyakov Evgeniy M. , Tsatsakis Aristides M. , Gurevich Leonid , Mezhuev Yaroslav O.
Published: June 2022

This paper deals with the development of polymeric nanocarriers based on amphiphilic copolymers of N‐vinyl‐2‐pyrrolidone and acrylic acid of various molecular weights synthesized through the AIBN‐initiated radical copolymerization of N‐vinyl‐2‐pyrrolidone and acrylic acid in the presence of n‐octadecyl mercaptan. The structure of the copolymers is characterized by 1Н NMR, 13С NMR, IR and MALDI‐TOF MS spectroscopy. It is shown that the length of the hydrophilic block defines the size of the nanoaggregates while impacting the steric stabilization efficiency and the probability of the interchain hydrogen bond formation. The hydrogen bonds formation between the residues of N‐vinyl‐2‐pyrrolidone and acrylic acid is in agreement with the reduction of the ζ‐potential of the nanoaggregates and the critical aggregation concentrations upon increasing the molecular weight. The presence of acrylic acid residues in the amphiphilic macromolecules leads to a higher affinity for doxorubicin and slow partial release of doxorubicin bonded with the aggregates’ corona, which is helpful for reducing its cardiac toxicity. Nanoaggregates with a paclitaxel‐loaded hydrophobic core are obtained, showing the possibility of dual loading. The amphiphilic copolymers of N‐vinyl‐2‐pyrrolidone and acrylic acid containing an n‐octadecyl thio end group are thus promising candidates for combination cancer therapy with immobilized anti‐cancer drugs, paclitaxel, and doxorubicin.
Fast four‐dimensional cone‐beam computed tomography reconstruction using deformable convolutional networks
Authors: Jiang Zhuoran , Chang Yushi , Zhang Zeyu , Yin Fang‐Fang , Ren Lei
Published: June 2022

Background

Although four‐dimensional cone‐beam computed tomography (4D‐CBCT) is valuable to provide onboard image guidance for radiotherapy of moving targets, it requires a long acquisition time to achieve sufficient image quality for target localization. To improve the utility, it is highly desirable to reduce the 4D‐CBCT scanning time while maintaining high‐quality images. Current motion‐compensated methods are limited by slow speed and compensation errors due to the severe intraphase undersampling.

Purpose

In this work, we aim to propose an alternative feature‐compensated method to realize the fast 4D‐CBCT with high‐quality images.

Methods

We proposed a feature‐compensated deformable convolutional network (FeaCo‐DCN) to perform interphase compensation in the latent feature space, which has not been explored by previous studies. In FeaCo‐DCN, encoding networks extract features from each phase, and then, features of other phases are deformed to those of the target phase via deformable convolutional networks. Finally, a decoding network combines and decodes features from all phases to yield high‐quality images of the target phase. The proposed FeaCo‐DCN was evaluated using lung cancer patient data.

Results

(1) FeaCo‐DCN generated high‐quality images with accurate and clear structures for a fast 4D‐CBCT scan; (2) 4D‐CBCT images reconstructed by FeaCo‐DCN achieved 3D tumor localization accuracy within 2.5 mm; (3) image reconstruction is nearly real time; and (4) FeaCo‐DCN achieved superior performance by all metrics compared to the top‐ranked techniques in the AAPM SPARE Challenge.

Conclusion

The proposed FeaCo‐DCN is effective and efficient in reconstructing 4D‐CBCT while reducing about 90% of the scanning time, which can be highly valuable for moving target localization in image‐guided radiotherapy.
Clinical trials in desmoid‐type fibromatosis in children and adults: A systematic review
Authors: van Maren Simone A. , van Noesel Max M. , Husson Olga , van der Graaf Winette T. A.
Published: June 2022

Desmoid‐type fibromatosis (DTF) is a rare locally aggressive soft tissue neoplasm, which occurs in children and adults, with a peak incidence in young adults. For the majority of the patients, DTF is a chronic and symptomatic disease, which affects health‐related quality of life. Systemic treatment regimens tend to differ for patients treated by pediatric oncologists compared to medical oncologists. This systematic review identified 14 clinical trials in children and adults with DTF. Tumor response and progression‐free survival rates varied widely between studies and study populations. Treatment choices for patients with DTF are based on a paucity of (randomized) trials. Treatment principles of DTF are similar in pediatric and adult oncology, but the treatment itself is different. This seems mostly driven by a lack of tyrosine kinase inhibitor (TKI) accessibility in pediatric oncology. An insufficient number of studies examined patient‐reported outcomes, which are extremely important for patients with a chronic disease like DTF.
Identification of RCC1–LCK as a novel fusion gene in pediatric erythroid sarcoma
Authors: Oya Satoru , Osone Shinya , Yoshida Masanori , Nishimoto Sota , Taura Yoshihiro , Yoshida Hideki , Miyachi Mitsuru , Inaba Tohru , Konishi Eiichi , Kato Motohiro , Imamura Toshihiko , Iehara Tomoko
Published: June 2022

Erythroid sarcoma is a very rare subtype of myeloid sarcoma with undetermined biological features. Here, we present an infant with a multifocal erythroid sarcoma, diagnosed because the tumor cells were positive for glycophorin A. After acute myeloid leukemia‐oriented chemotherapy and surgical resection followed by cord blood transplantation, he has successfully maintained complete remission without any late effects. Total transcriptome analysis of the tumor identified a novel fusion gene, RCC1–LCK, and high LCK expression levels, suggesting that LCK overexpression was involved in leukemogenesis in this case.
Environmentally sustainable chemical treatment of plant fibers for improved performance of polymeric composites
Authors: Das Partha Pratim , Manral Ankit , Ahmad Furkan , Sharma Bhasha , Chaudhary Vijay , Gupta Sumit , Gupta Pallav
Published: June 2022

The present study compares the results of two different chemical treatments of plant fibers reinforcement in terms of mechanical performance and their environmental impact considering sustainability. Jute/Hemp/Flax and their hybrid bidirectional mats were treated separately with two different chemicals namely sodium hydroxide (NaOH) and sodium bicarbonate (NaHCO3). The impact of the treatments on the mechanical performance of developed polymeric composites was found to be positive when compared to non‐treated fiber‐reinforced composites. Alkaline treatment showed better mechanical properties as compared to sodium bicarbonate treatment while using a low concentration solution, but the situation was reversed when a higher concentration solution was used. The present study also compares the pH value of the residue chemical solution after both the treatments which is a direct indicator of the acidic level present in the solution. Interestingly, the pH value of the residue chemical solution after the sodium bicarbonate treatment of the fibers was found in the neutral range indicating that the solution is not harmful to the environment and helps in maintaining sustainability while disposing of after the treatment. On the other hand, the ph value (measure using a pH meter) of the sodium hydroxide solution was in the strong alkaline indicating harmful effects in the disposing area. The environmentally friendly treatment of natural fibers with sodium bicarbonate could have a large commercial potential for polymeric composites for various applications.
Development of and insights from systems pharmacology models of antibody‐drug conjugates
Authors: Lam Inez , Pilla Reddy Venkatesh , Ball Kathryn , Arends Rosalinda H. , Mac Gabhann Feilim
Published: June 2022

Antibody‐drug conjugates (ADCs) have gained traction in the oncology space in the past few decades, with significant progress being made in recent years. Although the use of pharmacometric modeling is well‐established in the drug development process, there is an increasing need for a better quantitative biological understanding of the pharmacokinetic and pharmacodynamic relationships of these complex molecules. Quantitative systems pharmacology (QSP) approaches can assist in this endeavor; recent computational QSP models incorporate ADC‐specific mechanisms and use data‐driven simulations to predict experimental outcomes. Various modeling approaches and platforms have been developed at the in vitro, in vivo, and clinical scales, and can be further integrated to facilitate preclinical to clinical translation. These new tools can help researchers better understand the nature and mechanisms of these targeted therapies to help achieve a more favorable therapeutic window. This review delves into the world of systems pharmacology modeling of ADCs, discussing various modeling efforts in the field thus far.
Timing of induction of labour in the prevention of prolonged pregnancy: Systematic review with meta‐analysis
Authors: Geneen Louise J. , Gilbert James , Reeves Tim , Mainie Pramod , Maresh Michael , Smith Lisa , Wu Pensee , Parisaei Maryam
Published: June 2022

Objective

To update the systematic review which informed the National Institute for Health and Care Excellence guideline “Inducing Labour” (NG207), including additional data and analyses, and comparison with a recent individual patient data analysis of 41‐ versus 42‐week induction.

Search Strategy

Multiple database search (including Cochrane Central Register of Controlled Trials, MEDLINE, and Embase) from inception to 10th September 2021 for randomised controlled trials (RCTs) comparing different induction timing in uncomplicated singleton pregnancies.

Data Collection and Analysis

One reviewer screened, extracted, analysed, and assessed the quality/certainty of the evidence (using ROB1 and GRADE), with second reviewer verification.

Main Results

Five week‐to‐week comparisons, and one overall comparison (induction vs. delayed induction, 20 RCTs, n = 15 725 pregnant women) for assessment of predefined subgroups. Most data were for 41 versus 42 weeks and 39 versus 41 weeks: 10 times as many participants as the other week‐to‐week comparisons. There was evidence of an effect at 41 versus 42 weeks (five RCTs, n = 5819) in favour of 41‐week induction: fewer perinatal deaths and neonatal intensive care unit admissions (low‐to‐moderate certainty of the evidence); there was no evidence of an effect in either direction for the remaining outcomes (very‐low to moderate certainty). There was no evidence of an effect for outcomes reported for: 40 versus 42 weeks (three RCTs, n = 668, very‐low to low certainty); 39 versus 42 weeks (three RCTs, n = 1103, very‐low to moderate certainty); 39 versus 41 weeks (four RCTs, n = 7101, very‐low to low certainty); and 41/42 versus 43/44 weeks (four RCTs, n = 954, very‐low to low certainty).

Conclusion

The evidence supports offering induction at 41 + 0 weeks compared to 42 + 0 weeks to reduce adverse perinatal and obstetric outcomes.
Dual Regulation of Metal Doping and Adjusting Cut‐Off Voltage for MoSe2 to Achieve Reversible Sodium Storage
Authors: Hu Xuejiao , Zhu Ruiyu , Wang Beibei , Liu Xiaojie , Wang Hui
Published: June 2022

MoSe2, as a typical 2D material, possesses tremendous potential in Na‐ion batteries (SIBs) owing to larger interlayer distance, more favorable band gap structure, and higher theoretical specific capacity than other analogs. Nevertheless, the low intrinsic electronic conductivity and irreversible conversion of discharged products of Mo/Na2Se to MoSe2 seriously hamper its electrochemical performance. Herein, through a facile hydrothermal method combined with calcination process, Sn‐doped MoSe2 nanosheets grown on graphene substrate in the vertical direction are fabricated. Benefiting from the improved electronic conductivity contributed by the abundant defects and expanded interlamellar spacing of MoSe2 originated from Sn doping, combined with a smart strategy of raising discharge cut‐off voltage to 0.2 V during the actual performance testing for SIBs, the as‐fabricated anode material delivers superior Na‐ions storage performance in terms of electrons/ions transfer, reversible sodium storage as well as cycle stability. An ultra‐stable reversible specific capacity of 268.5 mAh g–1 at 1 A g–1 can be maintained after 1600 cycles. Moreover, the great sodium storage property in the SIB full‐cell system of the as‐obtained nanocomposite illustrates practical potential. Density functional theory calculation and in situ/ex situ measurements are employed to further reveal the storage mechanism and process of Na‐ions.