bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges of senior 8-year-program medical students’ scientific research in China
Authors: Wan Mengyao , Liu Shuang , Zhu Jiawei , Xiao Sulong , Yuan Lei , Lei Xiaokang , Lei Hao , Shi Xiaomin , You Wen , Ruan Gechong , Li Ji 
Published: April 2022

Abstract
Among the diverse medical education systems in China, the 8-year program is dedicated to cultivating physician scientists. Although the research ability of senior students in 8-year medical programs is a pivotal quality, it remains unclear. This study aimed to clarify the current status and challenges of students’ research experience, abilities, and outputs.
A multicenter cross-sectional study was conducted in 5 medical schools in northern China. Electronic questionnaires were sent to 235 randomly chosen fifth-grade or sixth-grade 8-year-program medical students. A total of 211 responses were collected and analyzed using SPSS 22.0.
Only 13.3% of participants chose research as their future career goal. Students generally felt that conducting research was stressful and difficult. The greatest obstacle was a lack of time due to heavy workloads. The 2 major motivations for research were graduation and/or future employment (75.8%) and research interest (24.2%). More than half of the students (142, 67.3%) had research experience by the time of the survey, among whom 84 students already had research outputs. A higher proportion of students with outputs was motivated by the requirements for graduation or employment compared to students without outputs (71.4% vs 55.2%, P
=
.046).
Senior 8-year-program medical students in China generally had high pressure to conduct research and devoted their efforts to overcome these challenges. More guidance and novel encouragement to enhance students’ initiative and interest in research could be provided by medical schools and educators in the future.
Septic cavernous sinus thrombosis after minor head trauma
Authors: Kim Jae-Myung , Kang Kyung Wook , Kim Hyunsoo , Lee Seung-Han , Kim Tae-Sun , Park Man-Seok 
Published: April 2022

Abstract

Rationale:
Septic cavernous sinus thrombosis (SCST) is a rare but life-threatening condition that commonly arises from infections, including paranasal sinusitis, otitis media, and skin infection. Meanwhile, head trauma as a predisposing factor of SCST has been scarcely reported. We report a case of SCST complicated by meningitis after minor head trauma, even in the absence of identifiable fractures.

Patient concerns and diagnosis:
A 77-year-old female presented with diplopia combined with ocular pain and headache lasting a week. She had a recent blunt head trauma 2 weeks before the diplopia onset. The trauma was not accompanied by identifiable skull fractures, bleeding, or loss of consciousness. Neurological examination revealed incomplete ptosis, eyelid swelling, and medial and vertical gaze limitations of both eyes. Gadolinium-enhanced brain magnetic resonance imaging demonstrated multifocal thrombotic filling defects, including those of the cavernous sinus, sinusitis involving the sphenoid and ethmoid sinuses, and otomastoiditis. The cerebrospinal fluid assay result was compatible with bacterial meningitis. A tentative diagnosis of SCST complicated by bacterial meningitis and multifocal cerebral venous thrombosis was made based on clinical, laboratory, and neuroradiologic findings.

Intervention:
Intravenous triple antibiotic therapy (vancomycin, ceftriaxone, and ampicillin) for 2 weeks combined with methylprednisolone (1 g/d for 5 days) was administered. Despite the initial treatment, carotid-cavernous fistula was newly developed during hospitalization. Therefore, coil embolization was performed successfully for the treatment of carotid-cavernous fistula.

Outcomes:
The symptoms of the patient including diplopia gradually improved during the 8-month follow-up period.

Lessons:
Minor head trauma is a rare but possible cause of SCST. Early recognition and prompt treatment are essential for improving outcomes. Moreover, close observation is warranted, even if apparent serious complications were absent during initial evaluations in minor head trauma.
Effects of Low-Frequency (0.5 Hz) and High-Frequency (10 Hz) Repetitive Transcranial Magnetic Stimulation on Neurological Function, Motor Function, and Excitability of Cortex in Ischemic Stroke Patients
Authors: Wang Chao , Zeng Qifan , Yuan Zhigang , Wang Wei , Shen Mei 
Published: April 2022

Background:
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique. The purpose of our study is to explore the effects of low-frequency (0.5 Hz) and high-frequency (10 Hz) rTMS on neurological function, motor function, and excitability of cortex in Chinese ischemic stroke patients.

Materials and Methods:
A total of 240 ischemic stroke patients were collected. The National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), motor-evoked potential (MEP) cortical latency, central motor conduction time (CMCT), Fugel-Meyer assessment (FMA), Berg balance scale (BBS), and modified Barthel index (MBI) scores were recorded.

Results:
After treatment, the NIHSS, mRS, MEP cortical latency, CMCT, FMA, BBS, and MBI scores of the high-frequency group and low-frequency group were significantly improved than the sham stimulation group, and the changes in the low-frequency group were more significant (adjusted P<0.05). Compared with the sham stimulation group, high-frequency stimulation reduced the NIHSS score by 9.5%, mRS score by 12.6%, MEP latency by 2.5%, and CMCT by 5.8%, and increased the upper limb FMA scale by 16.4%, lower limb FMA scale by 8.8%, BBS by 26.3%, and MBI by 9.3%, while low-frequency stimulation reduced the NIHSS score by 23.8%, mRS score by 25.3%, MEP Latency by 11.7%, and CMCT by 9.1%, and increased the upper limb FMA scale by 24.1%, lower limb FMA scale by 18.4%, BBS by 27.4%, and MBI by 23.7% in our cohort.

Conclusions:
Low-frequency rTMS is better than high-frequency rTMS stimulation in improving neurological function, motor function, and excitability of cortex in ischemic stroke.
18F-FDG PET/CT Appearance of Radiation-Induced Delayed Transverse Myelitis
Authors: Choudhury Sayak , Purandare Nilendu , Shah Sneha , Agrawal Archi , Rangarajan Venkatesh 
Published: April 2022

Abstract
Delayed-onset radiation-induced myelitis is a rare but serious complication of radiation exposure to the spinal cord. In this report, we describe the 18F-FDG PET/CT findings of radiation-induced myelitis in a patient with carcinoma of buccal mucosa treated with external beam radiotherapy.
High neutralizing activity against Omicron BA.2 can be induced by COVID-19 mRNA booster vaccination
Authors: Tjan Lidya Handayani , Furukawa Koichi , Kurahashi Yukiya , Sutandhio Silvia , Nishimura Mitsuhiro , Arii Jun , Mori Yasuko 
Published: April 2022

AbstractThe VOC of SARS-CoV-2, Omicron (BA.1, BA.1.1, BA.2, or BA.3), is associated with an increased risk of reinfection. BA.2 has become the next dominant variant worldwide. Although BA.2 infection has been shown to be mild illness, its high transmissibility will result in high numbers of cases. In response to the surge of Omicron BA.1 cases, booster vaccination was initiated in many countries. But there is limited evidence regarding the effectiveness of a booster vaccination against BA.2. We collected blood samples from 84 physicians at Kobe University Hospital, Japan, in January 2022 ∼7 months after they had received two BNT162b2 vaccinations and ∼2 weeks after their booster vaccination. We performed a serum neutralizing assay against BA.2 using authentic virus.Although most of the participants had no or a very low titer of neutralizing antibody against BA.2 at 7 months after two BNT162b2 vaccinations, the titer increased significantly at 2 weeks after the booster vaccination.
Wastewater to clinical case (WC) ratio of COVID-19 identifies insufficient clinical testing, onset of new variants of concern and population immunity in urban communities
Authors: D’Aoust Patrick M. , Tian Xin , Towhid Syeda Tasneem , Xiao Amy , Mercier Elisabeth , Hegazy Nada , Jia Jian-Jun , Wan Shen , Kabir Md Pervez , Fang Wanting , Fuzzen Meghan , Hasing Maria , Yang Minqing Ivy , Sun Jianxian , Plaza-Diaz Julio , Zhang Zhihao , Cowan Aaron , Eid Walaa , Stephenson Sean , Servos Mark R. , Wade Matthew J. , MacKenzie Alex E. , Peng Hui , Edwards Elizabeth A. , Pang Xiao-Li , Alm Eric J. , Graber Tyson E. , Delatolla Robert 
Published: April 2022

AbstractClinical testing has been the cornerstone of public health monitoring and infection control efforts in communities throughout the COVID-19 pandemic. With the extant and anticipated reduction of clinical testing as the disease moves into an endemic state, SARS-CoV-2 wastewater surveillance (WWS) is likely to have greater value as an important diagnostic tool to inform public health. As the widespread adoption of WWS is relatively new at the scale employed for COVID-19, interpretation of data, including the relationship to clinical cases, has yet to be standardized. An in-depth analysis of the metrics derived from WWS is required for public health units/agencies to interpret and utilize WWS-acquired data effectively and efficiently. In this study, the SARS-CoV-2 wastewater signal to clinical cases (WC) ratio was investigated across seven different cities in Canada over periods ranging from 8 to 21 months. Significant increases in the WC ratio occurred when clinical testing eligibility was modified to appointment-only testing, identifying a period of insufficient clinical testing in these communities. The WC ratio decreased significantly during the emergence of the Alpha variant of concern (VOC) in a relatively non-immunized community’s wastewater (40-60% allelic proportion), while a more muted decrease in the WC ratio signaled the emergence of the Delta VOC in a relatively well-immunized community’s wastewater (40-60% allelic proportion). Finally, a rapid and significant decrease in the WC ratio signaled the emergence of the Omicron VOC, likely because of the variant’s greater effectiveness at evading immunity, leading to a significant number of new reported clinical cases, even when vaccine-induced community immunity was high. The WC ratio, used as an additional monitoring metric, complements clinical case counts and wastewater signals as individual metrics in its ability to identify important epidemiological occurrences, adding value to WWS as a diagnostic technology during the COVID-19 pandemic and likely for future pandemics.
pH as an eco-evolutionary driver of priority effects
Authors: Chappell Callie R. , Dhami Manpreet K. , Bitter Mark C. , Czech Lucas , Paredes Sur Herrera , Eritano Katherine , Golden Lexi-Ann , Hsu Veronica , Kieschnick Clara , Rush Nicole , Fukami Tadashi 
Published: April 2022

AbstractPriority effects, where arrival order and initial relative abundance modulate local species interactions, can exert taxonomic, functional, and evolutionary influences on ecological communities by driving them to alternative states. It remains unclear if these wide-ranging consequences of priority effects can be explained systematically by a common underlying factor. Here, we identify such a factor in an empirical system. In a series of field and laboratory studies, we focus on how pH affects nectar-colonizing microbes and their interactions with plants and pollinators. In a field survey, we found that nectar microbial communities in a hummingbird-pollinated shrub, Diplacus aurantiacus, exhibited patterns indicative of alternative stable states through domination by either bacteria or yeasts within individual flowers. In laboratory experiments, Acinetobacter nectaris, the bacterium most commonly found in D. aurantiacus nectar, exerted a strongly negative priority effect against Metschnikowia reukaufii, the most common nectar-specialist yeast, by reducing nectar pH. This priority effect likely explains the mutually exclusive pattern of dominance found in the field survey. Furthermore, experimental evolution simulating hummingbird-assisted dispersal between flowers revealed that M. reukaufii could evolve rapidly to improve resistance against the priority effect if constantly exposed to A. nectaris-induced pH reduction. Finally, in a field experiment, we found that low nectar pH could reduce nectar consumption by hummingbirds, suggesting functional consequences of the pH-driven priority effect for plant reproduction. Taken together, these results show that it is possible to identify an overarching factor that governs the eco-evolutionary dynamics of priority effects across multiple levels of biological organization.
SUMOylation controls the rapid transcriptional reprogramming induced by anthracyclines in Acute Myeloid Leukemias
Authors: Boulanger Mathias , Kifagi Chamseddine , Ristic Marko , Gabellier Ludovic , Tempé Denis , Sigurdsson Jon-Otti , Kaoma Tony , Andrieu-Soler Charlotte , Forné Thierry , Soler Eric , Hicheri Yosr , Gueret Elise , Vallar Laurent , Olsen Jesper V , Cartron Guillaume , Piechaczyk Marc , Bossis Guillaume 
Published: April 2022

AbstractGenotoxicants have been used for decades as front-line therapies against cancer on the basis of their DNA-damaging actions. However, some of their non-DNA-damaging effects are also instrumental for killing dividing cells. We report here that the anthracycline Daunorubicin (DNR), one of the main drugs used to treat Acute Myeloid Leukemia (AML), induces broad transcriptional changes in AML cells before cell death induction. The regulated genes are particularly enriched in genes controlling cell proliferation and death, as well as inflammation and immunity. These transcriptional changes are preceded by DNR-dependent deSUMOylation of chromatin proteins, which limits both the positive and negative effects of DNR on transcription. Quantitative proteomics shows that proteins that are deSUMOylated in response to DNR are mostly transcription factors, transcriptional co-regulators and chromatin organizers. Among them, the CCCTC-binding factor CTCF is highly enriched at SUMO-binding sites found in cis-regulatory regions. This is notably the case at the promoter of the DNR-induced NFKB2 gene. Its induction is preceded by a SUMO-dependent reconfiguration of chromatin loops engaging its CTCF- and SUMO-bound promoter with distal cis-regulatory regions. Altogether, our work suggests that one of the earliest effects of DNR in AML cells is a SUMO-dependent transcriptional reprogramming.
Lagrange-NG: The next generation of Lagrange
Authors: Bettisworth Ben , Smith Stephen A. , Stamatakis Alexandros 
Published: April 2022

AbstractComputing ancestral ranges via the Dispersion Extinction and Cladogensis (DEC) model of biogeography is characterized by an exponential number of states relative to the number of regions considered. This is because the DEC model requires computing a large matrix exponential, which typically accounts for up to 80% of overall runtime. Therefore, the kinds of biogeographical analyses that can be conducted under the DEC model are limited by the number of regions under consideration. In this work, we present a completely redesigned efficient version of the popular tool Lagrange which is up to 2.5 times faster, which we call Lagrange-NG (Next Generation). We further reduce time-to-completion by introducing a multi-grained parallelization approach, achieving a total parallel speedup of 8.5 over Lagrange on a machine with 8 cores. In order to validate the correctness of Lagrange-NG, we also introduce a novel metric on range distributions for trees in order to assess the difference between any two range inferences. Finally, Lagrange-NG exhibits substantially higher adherence to coding quality standards. It improves a respective software quality indicator as implemented in the SoftWipe tool from average (5.5; Lagrange) to high (7.8; Lagrange-NG). Lagrange-NG is freely available under GPL2.
Dynamics and Energetics of Bottlenose Dolphins (Tursiops truncatus) Fluke-and-Glide Gait
Authors: Zhang Ding , Wang Yifan , Gabaldon Joaquin , Lauderdale Lisa K. , Miller Lance J. , Barton Kira , Shorter Kenneth Alex 
Published: April 2022

ABSTRACTIntermittent locomotion composed of periods of active flapping/stroking followed by inactive gliding has been observed with species that inhabit both aerial and marine environments. However, studies on the energetic benefits of a fluke-and-glide (FG) gait during horizontal locomotion are limited for dolphins. This work presents a physics-based model of FG gait and analysis of the associated costs of transport of bottlenose dolphins (Tursiops truncatus). New estimates of gliding drag coefficients for the model were estimated experimentally from free-swimming bottlenose dolphins. The data-driven approach used kinematic measurement from 84 hours of biologging tag data collected from 3 animals to estimate the coefficients. A set of 532 qualified gliding events were automatically extracted for gliding drag coefficient estimation, and an additional 783 FG bouts were parameterized and used to inform the model-based dynamic analysis. Experimental results indicate that FG gait was preferred at speeds around 2.2 - 2.7 m/s. Observed FG bouts had an average duty factor of 0.45 and gliding duration of 5 sec. The average associated metabolic cost of transport (COT) and mechanical cost of transport (MECOT) of FG gait are 2.53 and 0.35 J · m−1 · kg−1 at the preferred speeds. This corresponded to an 18.9% and 27.1% reduction in cost when compared to modeled continuous fluking gait at the same reference speed. Average thrust was positively correlated with fluking frequency and amplitude as animals accelerated during the FG bouts. While fluking frequency and amplitude were negatively correlated for a given thrust range. These results support the supposition that FG gait enhances the horizontal swimming efficiency of bottlenose dolphins and provides new dynamical insights into the gait of these animals.
From motif to function: Inferring the functions of long zinc finger proteins through combinatorial selection
Authors: Zuo Zheng 
Published: April 2022

ABSTRACTC2H2 zinc finger proteins (ZFPs) comprise of the largest group of DNA-binding proteins in human genome, and many of them contain long, tandem array of fingers, making the motif discovery, prediction of in vivo cis-regulatory elements (CREs), and understanding their functions particularly challenging. Previous work established that due to the dependent recognition between sub-motifs, the simple, additive recognition model impedes motif discovery and compromises our understanding about how ZFPs work. This work uses ZFP3, a 13-finger long ZFP with no known function, as case example to address the reverse question---given the full-length motif learned through in vitro experiments, like Spec-seq and HT-SELEX, how to reliably identify its in vivo cis-regulatory elements (CREs) and further predict this gene’s functions. Through sorting of all possible sites within the ChIP-seq peaks with similar predicted binding energy into groups and comparing the aggregate ChIP-seq signals between groups, it is evident that either its full-length or individual sub-motif alone fails to correctly identify all high-affinity specific sites without false-positives, thus it is necessary to revise current algorithm, and use both the core and upstream motifs as separate components to improve the prediction accuracy. Furthermore, significant number of regulatory elements of ZFP3 are found to be proximal to genes associated with microtubules organization and ciliogenesis, which coincides with the fact that ZFP3 is specifically upregulated in multiple ciliated cells. At last, local chromatin accessibility and active chromatin marks like H3K27ac are found to positively associate with the differential binding of ZFP3 between tested cell lines. Overall, this work establishes a novel “From motif to function” strategy for long ZFPs, and the data analysis workflows are implemented through R package TFCookbook for reuse onto other ZFPs.
moRphology - dEep Learning Imaging Cells (RELIC) - to Differentiate Between Normal and Pathological Kidney Exfoliated Cells
Authors: Habibalahi Abbas , Campbell Jared M. , Mahbub Saabah B. , Anwer Ayad G. , Nguyen Long T. , Gill Anthony J , Wong Muh Geot , Chou Angela , Pollock Carol A. , Saad Sonia , Goldys Ewa M. 
Published: April 2022

AbstractChronic kidney disease (CKD) is characterised by progressive loss of kidney function leading to kidney failure. Significant kidney damage can occur before symptoms are detected. Currently, kidney tissue biopsy is the gold standard for evaluation of renal damage and CKD severity. This study explores how to precisely quantify morphology characteristics of kidney cells exfoliated into urine, with a view to establish a future urine-based non-invasive diagnostic for CKD. We report the development of a novel deep learning method, which was able to discover a RELIC (moRphology dEep Learning Imaging Cells) signature that can differentiate between kidney cells exfoliated in human urine of and CKD patients with varying degree of kidney damage and non-CKD controls. Exfoliated proximal tubule cells (PTCs) originating from kidneys were isolated from the urine of patients with different levels of kidney damage using previously published methods. An advanced combination of artificial intelligence techniques, deep learning, swarm intelligence, and discriminative analysis was used to discover a RELIC signature in brightfield microscopy images of exfoliated PTCs. Kidney damage in the study subjects was characterised by assessing kidney tissues obtained through a nephrectomy or kidney biopsy. A special deep learning algorithm was developed and trained to create a predictive tool. The algorithm was then used to analyse data from patients with normal and fibrotic kidneys. Data were then classified according to different groups (healthy or fibrosis) and clustering of the training and validation cells was determined for model validation. We developed a novel deep learning method, to obtain RELIC signatures and identify specific deep morphological features which can be used to differentiate urinary PTC cells shed by people with CKD (confirmed by tissue histology obtained from an invasive kidney biopsy) from those without CKD, with a discriminatory accuracy of 82%. We identified a RELIC signature which can be used on a collection of bright field images of exfoliated urinary PTCs to create a predictive tool and differentiate between normal and pathological kidney cells. This study, for the first time, provides a proof of concept that urinary exfoliated tubule cells in patients with kidney fibrosis and healthy controls differ in appearance (morphology) as observed under a basic brightfield microscope. The results suggest that morphological signatures of exfoliated PTCs have the potential to serve as a non-invasive marker of kidney fibrosis.