bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous bladder urinary oxygen tension as a new tool to monitor medullary oxygenation in the critically ill
Authors: Hu Raymond T. , Lankadeva Yugeesh R. , Yanase Fumitake , Osawa Eduardo A. , Evans Roger G. , Bellomo Rinaldo 
Published: December 2022

AbstractAcute kidney injury (AKI) is common in the critically ill. Inadequate renal medullary tissue oxygenation has been linked to its pathogenesis. Moreover, renal medullary tissue hypoxia can be detected before biochemical evidence of AKI in large mammalian models of critical illness. This justifies medullary hypoxia as a pathophysiological biomarker for early detection of impending AKI, thereby providing an opportunity to avert its evolution. Evidence from both animal and human studies supports the view that non-invasively measured bladder urinary oxygen tension (PuO2) can provide a reliable estimate of renal medullary tissue oxygen tension (tPO2), which can only be measured invasively. Furthermore, therapies that modify medullary tPO2 produce corresponding changes in bladder PuO2. Clinical studies have shown that bladder PuO2 correlates with cardiac output, and that it increases in response to elevated cardiopulmonary bypass (CPB) flow and mean arterial pressure. Clinical observational studies in patients undergoing cardiac surgery involving CPB have shown that bladder PuO2 has prognostic value for subsequent AKI. Thus, continuous bladder PuO2 holds promise as a new clinical tool for monitoring the adequacy of renal medullary oxygenation, with its implications for the recognition and prevention of medullary hypoxia and thus AKI.
Exploring functional protein covariation across single cells using nPOP
Authors: Leduc Andrew , Huffman R. Gray , Cantlon Joshua , Khan Saad , Slavov Nikolai 
Published: December 2022

Abstract
Background
Many biological processes, such as cell division cycle and drug resistance, are reflected in protein covariation across single cells. This covariation can be quantified and interpreted by single-cell mass spectrometry with sufficiently high throughput and accuracy.

Results
Here, we describe nPOP, a method that enables simultaneous sample preparation of thousands of single cells, including lysing, digesting, and labeling individual cells in volumes of 8–20 nl. nPOP uses piezo acoustic dispensing to isolate individual cells in 300 pl volumes and performs all subsequent sample preparation steps in small droplets on a fluorocarbon-coated glass slide. Protein covariation analysis identifies cell cycle dynamics that are similar and dynamics that differ between cell types, even within subpopulations of melanoma cells delineated by markers for drug resistance priming. Melanoma cells expressing these markers accumulate in the G1 phase of the cell cycle, display distinct protein covariation across the cell cycle, accumulate glycogen, and have lower abundance of glycolytic enzymes. The non-primed melanoma cells exhibit gradients of protein abundance, suggesting transition states. Within this subpopulation, proteins functioning in oxidative phosphorylation covary with each other and inversely with proteins functioning in glycolysis. This protein covariation suggests divergent reliance on energy sources and its association with other biological functions. These results are validated by different mass spectrometry methods.

Conclusions
nPOP enables flexible, automated, and highly parallelized sample preparation for single-cell proteomics. This allows for quantifying protein covariation across thousands of single cells and revealing functionally concerted biological differences between closely related cell states. Support for nPOP is available at https://scp.slavovlab.net/nPOP.
How do we know a treatment is good enough? A survey of non-inferiority trials
Authors: Attard Naomi , Totton Nikki , Gillies Katie , Goulao Beatriz 
Published: December 2022

Abstract
Background
Non-inferiority and equivalence trials aim to determine whether a new treatment is good enough (non-inferior) or as good as (equivalent to) another treatment. To inform the decision about non-inferiority or equivalence, a margin is used. We aimed to identify the current methods used to determine non-inferiority or equivalence margins, as well as the main challenges and suggestions from trialists.

Methods
We developed an online questionnaire that included both closed and open-ended questions about methods to elicit non-inferiority or equivalence margins, underlying principles, and challenges and suggestions for improvement. We recruited trialists with experience of determining a margin by contacting corresponding authors for non-inferiority or equivalence trials. We used descriptive statistics and content analysis to identify categories in qualitative data.

Results
We had forty-one responses, all from non-inferiority trials. More than half of the trials were non-pharmacological (n = 21, 51%), and the most common primary outcome was clinical (n = 29, 71%). The two most used methods to determine the margin were as follows: a review of the evidence base (n = 27, 66%) and opinion seeking methods (n = 24, 59%). From those using reviews, the majority used systematic reviews or reviews of multiple RCTs to determine the margin (n = 17, 63%). From those using opinion seeking methods, the majority involved clinicians with or without other professionals (n = 19, 79%). Respondents reported that patients’ opinions on the margin were sought in four trials (16%). Median confidence in overall quality of the margin was 5 out of 7 (maximum confidence); however, around a quarter of the respondents were “completely unconfident” that the margin reflected patient’s views. We identified “stakeholder involvement” as the most common category to determine respondent’s confidence in the quality of the margins and whether it reflected stakeholder’s views. The most common suggestion to improve the definition of margins was “development of methods to involve stakeholders,” and the most common challenge identified was “communication of margins.”

Conclusions
Responders highlighted the need for clearer guidelines on defining a margin, more and better stakeholder involvement in its selection, and better communication tools that enable discussions about non-inferiority trials with stakeholders. Future research should focus on developing best practice recommendations.
A savings intervention to reduce men’s engagement in HIV risk behaviors: study protocol for a randomized controlled trial
Authors: Egbe Teniola I. , Omollo Ouma Dan , Wesonga Julius Oduor , Bair Elizabeth F. , Chakrabarti Averi , Putt Mary E. , Celum Connie L. , Camlin Carol S. , Napierala Sue , Agot Kawango , Thirumurthy Harsha 
Published: December 2022

Abstract
Background
In much of eastern and southern Africa, the incidence of HIV and other sexually transmitted infections (STIs) remains high despite the scale-up of promising biomedical and behavioral interventions. Studies have documented the crucial role of transactional sex—the exchange of money, material support, or goods, in sexual relationships—and heavy alcohol use in contributing to men’s and women’s health outcomes. Existing policy responses to this challenge have largely focused on women, through the provision of pre-exposure prophylaxis (PrEP) or structural interventions such as education subsidies and cash transfers. However, the effectiveness of these interventions has been hindered by the relative lack of interventions and programs targeting men’s behavior. We describe the protocol for a study that will test an economic intervention designed to reduce men’s engagement in HIV/STI-related risk behaviors in Kenya.

Methods
We will conduct a randomized controlled trial among income-earning men in Kenya who are aged 18–39 years and self-report alcohol use and engagement in transactional sex. The study will enroll 1500 participants and randomize them to a control group or savings group. The savings group will receive access to a savings account that includes lottery-based incentives to save money regularly, opportunities to develop savings goals/strategies, and text message reminders about their savings goals. The control group will receive basic health education. Over a period of 24 months, we will collect qualitative and quantitative data from participants and a subset of their female partners. Participants will also be tested for HIV and other STIs at baseline, 12, and 24 months.

Discussion
The findings from this study have the potential to address a missing element of HIV/STI prevention efforts in sub-Saharan Africa by promoting upstream and forward-looking behavior and reducing the risk of acquiring HIV/STIs in a high HIV/STI burden setting. If this study is effective, it is an innovative approach that could be scaled up and could have great potential for scientific and public health impact in Kenya.

Trial registration
ClinicalTrials.govNCT05385484. Registered on May 23, 2022
Footwear and insole design parameters to prevent occurrence and recurrence of neuropathic plantar forefoot ulcers in patients with diabetes: a series of N-of-1 trial study protocol
Authors: Ahmed Sayed , Butterworth Paul , Barwick Alex , Sharma Anita , Hasan Md Zobaer , Nancarrow Susan 
Published: December 2022

AbstractBackgroundFoot complications occur in conjunction with poorly controlled diabetes. Plantar forefoot ulceration contributes to partial amputation in unstable diabetics, and the risk increases with concomitant neuropathy. Reducing peak plantar forefoot pressure reduces ulcer occurrence and recurrence. Footwear and insoles are used to offload the neuropathic foot, but the success of offloading is dependent on patient adherence. This study aims to determine which design and modification features of footwear and insoles improve forefoot plantar pressure offloading and adherence in people with diabetes and neuropathy.MethodsThis study, involving a series of N-of-1 trials, included 21 participants who had a history of neuropathic plantar forefoot ulcers. Participants were recruited from two public hospitals and one private podiatry clinic in Sydney, New South Wales, Australia. This trial is non-randomised and unblinded. Participants will be recruited from three sites, including two high-risk foot services and a private podiatry clinic in Sydney, Australia. Mobilemat™ and F-Scan® plantar pressure mapping systems by TekScan® (Boston, USA) will be used to measure barefoot and in-shoe plantar pressures. Participants’ self-reports will be used to quantify the wearing period over a certain period of between 2 and 4 weeks during the trial. Participant preference toward footwear, insole design and quality-of-life-related information will be collected and analysed. The descriptive and inferential statistical analyses will be performed using IBM SPSS Statistics (version 27). And the software NVivo (version 12) will be utilised for the qualitative data analysis.DiscussionThis is the first trial assessing footwear and insole interventions in people with diabetes by using a series of N-of-1 trials. Reporting self-declared wearing periods and participants’ preferences on footwear style and aesthetics are the important approaches for this trial. Patient-centric device designs are the key to therapeutic outcomes, and this study is designed with that strategy in mind.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000699965p. Registered on June 23, 2020
The α-mating factor secretion signals and endogenous signal peptides for recombinant protein secretion in Komagataella phaffii
Authors: Zou Chenwei , Lu Lingfang , Wang Shengyan , Zhang Chenshan , Chen Xuequn , Lin Yao , Huang Yide 
Published: December 2022

Abstract
Background
The budding yeast Komagataella phaffii (Pichia pastoris) is widely employed to secrete proteins of academic and industrial interest. For secretory proteins, signal peptides are the sorting signal to direct proteins from cytosol to extracellular matrix, and their secretion efficiency directly impacts the yields of the targeted proteins in fermentation broth. Although the α-mating factor (MF) secretion signal from S. cerevisiae, the most common and widely used signal sequence for protein secretion, works in most cases, limitation exists as some proteins cannot be secreted efficiently. As the optimal choice of secretion signals is often protein specific, more secretion signals need to be developed to augment protein expression levels in K. phaffii.

Results
In this study, the secretion efficiency of 40 α-MF secretion signals from various yeast species and 32 endogenous signal peptides from K. phaffii were investigated using enhanced green fluorescent protein (EGFP) as the model protein. All of the evaluated α-MF secretion signals successfully directed EGFP secretion except for the secretion signals of the yeast D. hansenii CBS767 and H. opuntiae. The secretion efficiency of α-MF secretion signal from Wickerhamomyces ciferrii was higher than that from S. cerevisiae. 24 out of 32 endogenous signal peptides successfully mediated EGFP secretion. The signal peptides of chr3_1145 and FragB_0048 had similar efficiency to S. cerevisiae α-MF secretion signal for EGFP secretion and expression.

Conclusions
The screened α-MF secretion signals and endogenous signal peptides in this study confer an abundance of signal peptide selection for efficient secretion and expression of heterologous proteins in K. phaffii.
An overview of the trypanosomatid (Kinetoplastida: Trypanosomatidae) parasites infecting several mammal species in Colombia
Authors: Castillo-Castañeda Adriana C. , Patiño Luz H. , Zuñiga Maria Fernanda , Cantillo-Barraza Omar , Ayala Martha S. , Segura Maryi , Bautista Jessica , Urbano Plutarco , Jaimes-Dueñez Jeiczon , Ramírez Juan David 
Published: December 2022

Abstract
Background
Trypanosomatids are among the most critical parasites for public health due to their impact on human, animal, and plant health. Diseases associated with these pathogens manifest mainly in poor and vulnerable populations, where social, environmental, and biological factors modulate the case incidence and geographical distribution.

Methods
We used Sanger and amplicon-based next-generation sequencing (NGS) in samples from different mammals to identify trypanosomatid infections in several departments in Colombia. A total of 174 DNA samples (18 humans, 83 dogs, and 73 wild mammals) were analyzed by conventional PCR using a fragment of the heat shock protein 70 (Hsp70) gene and Sanger sequenced the positive samples. Twenty-seven samples were sent for amplicon-based NGS using the same gene fragment. Data obtained were used to perform diversity analyses.

Results
One hundred and thirteen samples were positive for PCR by Hsp70 fragment; these corresponded to 22.1% Leishmania spp., 18.6% L. amazonensis, 9.7% L. braziliensis, 14.2% L. infantum, 8% L. panamensis, and 27.4% Trypanosoma cruzi. Comparison of the identified species by the two sequencing technologies used resulted in 97% concordance. Alpha and beta diversity indices were significant, mainly for dogs; there was an interesting index of coinfection events in the analyzed samples: different Leishmania species and the simultaneous presence of T. cruzi and even T. rangeli in one of the samples analyzed. Moreover, a low presence of L. braziliensis was observed in samples from wild mammals. Interestingly, to our knowledge, this is the first report of Leishmania detection in Hydrochaeris hydrochaeris (capybara) in Colombia.

Conclusions
The Hsp70 fragment used in this study is an optimal molecular marker for trypanosomatid identification in many hosts and allows the identification of different species in the same sample when amplicon-based sequencing is used. However, the use of this fragment for molecular diagnosis through conventional PCR should be carefully interpreted because of this same capacity to identify several parasites. This point is of pivotal importance in highly endemic countries across South America because of the co-circulation of different genera from the Trypanosomatidae family. The findings show an interesting starting point for One Health approaches in which coevolution and vector-host interactions can be studied.

Graphical Abstract
Low disease activity of microscopic polyangiitis in patients with anti-myosin light chain 6 antibody that disrupts actin rearrangement necessary for neutrophil extracellular trap formation
Authors: Yoshinari Miku , Nishibata Yuka , Masuda Sakiko , Nakazawa Daigo , Tomaru Utano , Arimura Yoshihiro , Amano Koichi , Yuzawa Yukio , Sada Ken-Ei , Atsumi Tatsuya , Dobashi Hiroaki , Hasegawa Hitoshi , Harigai Masayoshi , Matsuo Seiichi , Makino Hirofumi , Ishizu Akihiro 
Published: December 2022

Abstract
Background
Neutrophil extracellular traps (NETs) are critically involved in microscopic polyangiitis (MPA) pathogenesis, and some patients with MPA possess anti-NET antibody (ANETA). Anti-myosin light chain 6 (MYL6) antibody is an ANETA that affects NETs. This study aimed to determine the significance of anti-MYL6 antibody in MPA.

Methods
The influence of anti-MYL6 antibody on NET formation and actin rearrangement necessary for NET formation was assessed by fluorescent staining. An enzyme-linked immunosorbent assay was established to detect serum anti-MYL6 antibody, and the prevalence of this antibody in MPA was determined. Furthermore, the disease activity and response to remission-induction therapy of MPA were compared between anti-MYL6 antibody-positive and anti-MYL6 antibody-negative MPA patients.

Results
Anti-MYL6 antibody disrupted G-actin polymerization into F-actin, suppressing phorbol 12-myristate 13-acetate-induced NET formation. Serum anti-MYL6 antibody was detected in 7 of 59 patients with MPA. The Birmingham vasculitis activity score (BVAS) of anti-MYL6 antibody-positive MPA patients was significantly lower than anti-MYL6 antibody-negative MPA patients. Among the nine BVAS evaluation items, the cutaneous, cardiovascular, and nervous system scores of anti-MYL6 antibody-positive MPA patients were significantly lower than anti-MYL6 antibody-negative MPA patients, although other items, including the renal and chest scores, were equivalent between the two groups. The proportion of patients with remission 6 months after initiation of remission-induction therapy in anti-MYL6 antibody-positive MPA patients was significantly higher than in anti-MYL6 antibody-negative MPA patients.

Conclusions
Collective findings suggested that anti-MYL6 antibody disrupted actin rearrangement necessary for NET formation and could reduce the disease activity of MPA.
A fast continuous time approach with time scaling for nonsmooth convex optimization
Authors: Boţ Radu Ioan , Karapetyants Mikhail A. 
Published: December 2022

AbstractIn a Hilbert setting, we study the convergence properties of the second order in time dynamical system combining viscous and Hessian-driven damping with time scaling in relation to the minimization of a nonsmooth and convex function. The system is formulated in terms of the gradient of the Moreau envelope of the objective function with a time-dependent parameter. We show fast convergence rates for the Moreau envelope, its gradient along the trajectory, and also for the system velocity. From here, we derive fast convergence rates for the objective function along a path which is the image of the trajectory of the system through the proximal operator of the first. Moreover, we prove the weak convergence of the trajectory of the system to a global minimizer of the objective function. Finally, we provide multiple numerical examples illustrating the theoretical results.
Quantifying “local food” online and social media in the United States for 2018–2021
Authors: Jung Jinho , Tao Jingjing , Widmar Nicole Olynk 
Published: December 2022

Abstract
Background
Interest in local food has been growing, driven by increased attention from consumers, supporting policies, and interest in offering supply by local producers. Nonetheless, a definition of “local food” remains elusive, varying with purposes, geographies, and perceptions. This study quantifies online media mentioning local food in 2018–2021 using online and social media listening and analytics. In addition, a sub-search devoted to local food security and access was conducted due to a high proportion of mentions devoted to food security in the initial search. Variations in mentions and net sentiment quantified for individual US states are also presented.

Results
The local food pantry sub-search arose after finding a large share of the general local food media was referencing local food access rather than production or other topics. The interest in local food access was more apparent during crises periods, such as the COVID-19 pandemic, during which even a larger portion of mentions are devoted to the local food pantry sub-search topic. Mentions quantified from the sub-search are mostly expressing concerns about worsened food insecurity during the pandemic and encouraging others to do things like donate food to local pantries.

Conclusions
Online and social media can play an important role towards active communication in local communities on topics, such as food availability and access. In addition, online media can facilitate more efficient emergency management.
Circadian phase advances in children during camping life according to the natural light-dark cycle
Authors: Eto Taisuke , Kitamura Shingo , Nishimura Kana , Takeoka Kota , Nishimura Yuki , Lee Sang-il , Ohashi Michihiro , Shikano Akiko , Noi Shingo , Higuchi Shigekazu 
Published: December 2022

Abstract
Background
It is known that the circadian rhythm phase in adults can be advanced in a natural light-dark cycle without electrical lighting. However, the effect of advanced sleep-wake timing according to the natural light-dark cycle on children’s circadian phase is unclear. We investigated the effects of approximately 2 weeks of camping life with little access to artificial lighting on children’s circadian phases. We also conducted an exploratory examination on the effects of wake time according to natural sunrise time on the manner of the advance of their circadian phases.

Methods
Twenty-one healthy children (mean ± SD age, 10.6 ± 1.4 years) participated in a camping program with wake time (4:00) being earlier than sunrise time (EW condition), and 21 healthy children (10.4 ± 1.1 years) participated in a camping program with wake time (5:00) being almost matched to sunrise time (SW condition). Salivary dim light melatonin onset (DLMO) before the camping program and that after approximately 2 weeks of camping were compared.

Results
DLMO was advanced by approximately 2 h after the camping program compared with the circadian phase in daily life in both conditions. In addition, the advances in DLMO were significantly correlated with mid-sleep points before the camp in both conditions (EW: r = 0.72, p < 0.01, SW: r = 0.70, p < 0.01). These correlations mean that the phase advance was greater for the children with delayed sleep habits in daily life. Furthermore, in the EW condition, mean DLMO after the camp (18:09 ± 0:33 h) was earlier than natural sunset time and there was no significant decrease in interindividual variability in DLMO. On the other hand, in the SW condition, mean DLMO after the camp (18:43 ± 0:20 h) matched natural sunset time and interindividual variability in DLMO was significantly lower than that before the camp.

Conclusions
Camping with advanced sleep and wake timing under natural sunlight advances children’s circadian phases. However, DLMO earlier than sunset in an early waking condition may lead to large interindividual variability in the circadian rhythm phase.