bluuebunny/crossref_metadata_2025 huggingface dataset:
N07 JAKne: JAK inhibitor associated acne, a real-life single-center experience
Authors: De Dycker E , Vermeire S , Ferrante M , Lambrechts T , Paps A , Geens P , Loddewijkx E , Sabino J , Hillary T , Verstockt B
Published: January 2024

Background

Three Janus kinase (JAK) inhibitors, tofacitinib (TFC), filgotinib (FIL) and upadacitinib (UPA), have been approved for treatment of Crohn’s disease (CD) and/or ulcerative colitis (UC). During the IBD registrational trials, acne was reported as adverse event (AE) in 5-7% of UPA treated patients, but not in the FIL and TFC programs. Hence, we assessed the prevalence of JAK inhibitor associated acne in a real-life cohort.

Methods

All patients initiating JAK inhibitors for active moderate-to-severe CD or UC at our center were included. Patients were prospectively monitored at prespecified timepoints, and specifically assessed for AEs including acne. Affected patients completed a visual analogue scale (VAS) to assess the impact of acne on their quality of life. All pictures of skin lesions were assessed by a dermatologist specialized in inflammatory skin diseases.

Results

In total, 46 patients initiated TFC, 40 FIL and 79 UPA. None of the TFC or FIL treated patients reported new onset of acne. Instead, 17 (21.5%) patients (9 CD, 8 UC; median [IQR] age 28.2 [25.2-45.0]; 47.1% female) spontaneously reported acne during UPA therapy. Most (89.5%) reported new onset of acne, while 2 (10.5%) mentioned a deterioration of existing acne during UPA induction. Previous acne during adolescence was reported by 46.2%. Lesions were present in the face (82.3%), back (23.5%), chest (23.5%) and scalp (11.8%). The acne phenotype included inflammatory papules in all patients, but also pustules (66.7%), nodules (33.3%), cysts (11.1%) and comedones (11.1%) were observed. A median VAS score of 5.5 [5.0-7.0] highlighted the impact on the patient’s quality of life, though no patient interrupted UPA due to acne. Six (35.2%) patients were referred to a dermatologist for acne. Most patients (82.4%) received topical skin therapy during UPA induction based on a standard operation procedure approved by the dermatologist and communicated via the IBD nurses. Three patients (17.6%) received antibiotics during UPA induction because of acne. During UPA maintenance, 5 patients (29.4%) reported resolution of skin problems with only 1 requiring continued skin therapy. Ten patients (58.7%) continued topical skin therapy during maintenance, with 4 of them requiring continued antibiotic treatment for at least 3 months. A single patient was deescalated from UPA 30mg to 15mg QD because of severe acne, with little improvement.

Conclusion

In this real-world experience, JAK inhibitor associated acne was uniquely linked to UPA, occurring in one fifth of patients. This is more prevalent than observed in the registrational trials. Awareness and patient education are therefore important, as well as early referral to the dermatologist for appropriate treatment.
N24 Supporting psychosocial and emotional wellbeing and building resilience in family members of people with IBD: a co-design study
Authors: Thapwong P , Norton C , Rowland E , Czuber-Dochan W
Published: January 2024

Background

IBD affects the quality of life (QoL) of both the patient and their family members. Our previous systematic review and qualitative research study found that family members of IBD patients express a need for improved information about IBD, networking opportunities, and increased access to support services such as IBD nurses, counsellors, or psychologists. While existing studies recognise the challenges faced by family members, there is a lack of interventions to address their psychosocial and emotional burdens. Therefore, this study aims to co-design and develop an intervention to support family members’ psychosocial and emotional wellbeing and build familial and individual resilience.

Methods

The study employed co-design approach informed by Design Thinking to explore family members’ needs, prioritise problems, and generate ideas for developing the new intervention. The co-design process comprised two sequential online workshops with individuals with IBD (n=4), family members (n=9), and IBD nurses (n=2). Workshop data were recorded in both video and audio formats, and transcribed verbatim. Reflexive thematic analysis was used to analyse the data.

Results

The study identified two priority areas for supporting family members of individuals with IBD: information and psychosocial support. Within these domains, specific solutions were pinpointed: (1) Improving access to information related to IBD and facilitating easier adaptation to living with the condition — achievable through educational materials, online resources, or support groups. (2) Increasing opportunities for networking and peer support, feasible through online forums, support groups, or social events. (3) Enhancing access to professional support services, such as counselling or therapy, to provide coping mechanisms and necessary emotional support. Additionally, a logic model and a prototype for a web-based online resource, aimed at supporting psychosocial and emotional wellbeing, were developed.

Conclusion

This co-design process delineated support priorities for family members of people with IBD, as well as offering suggestions for interventions aimed at fostering family members’ psychosocial and emotional wellbeing while promoting familial and individual resilience. We now plan to test this novel intervention in a feasibility study.
N29 Patient evaluation of digital IBD care in patient initiated follow up pathway using MyIBD Care app and home calprotectin test
Authors: Whitehead E , Schranz J , Peaks H , Abbie F , Turnbull J , Robertson H , Sebastian S
Published: January 2024

Background

Remote patient monitoring via web applications has been reported to have benefits with improvement in patient-reported quality of life, medication adherence, and decreased heath care costs. Mobile applications can be used for symptom reporting and this along with home biomarker testing can facilitate patient initiated follow up. There remain uncertainties in the acceptance of digital technologies in routine follow up care among IBD patients. We aimed to survey the pilot users of MyIBD care app and CalproSmart home calprotectin monitoring in an IBD cohort

Methods

Patients participating in the patient initiated follow up (PIFU) cohort in IBD Home digital care pathway at a tertiary IBD referral centre were included in this pilot survey before full roll out of the programme. Patients were given detailed written and electronic information about the pathway before signing up. Predefined survey questions were administered using electronic in app methodology. The survey questions were ranked in Likert scale from strongly agree, agree, neither agree or disagree, disagree and strongly disagree. Data reported as proportion of responses to each category.

Results

132 surveys were collected and analysed. Ninety three percent of responses understood the rationale for their inclusion to the digital pathway. Confidence in contacting the IBD team through digital pathway was reported in 89% of responses and 68% felt more in control of own condition. Eight six percent of patients understood the requirements for completing patient reported outcome measures and home calprotectin test while in the pathway and also felt confident in taking home calprotectin test. However only 44% felt closer to the clinical care team with the pathway.

Conclusion

Digital pathway incorporating a patient initiated follow up and self-monitoring is acceptable to IBD patients in stable remission with high satisfaction scores in all domains
ECCO Grant Untangling the gut phagosome dynamics of the relapse/remission cycle in ulcerative colitis
Authors: Kulecka M , Claesson M , Shkoporov A
Published: January 2024

Background and Aims

The course of ulcerative colitis (UC) is usually characterized by intertwining periods of remission and relapse. Most microbiome UC studies focus on the gut bacteriome. However, recent studies on animal models suggest that phage-mediated bacterial cell lysis may play a role in sustaining gut inflammation, proving the phageome (collection of bacteriophages) should not be ignored in this disease. Therefore, this project aims to: 1) characterize the gut phageome of patients with UC who suffer from frequent relapses, 2) compare temporal dynamics of gut the phageome between patients and healthy controls, 3) To model interactions between bacteriome, mycobiome, phageome on one hand, and lifestyle factors (diet, stress levels, medication) on the other 4) To infer host status (relapse versus remission of the disease) based on phageome composition, and using interactions inferred in Objective 3.

Methods

The cohort comprises 24 patients with UC (14 of whom suffered from relapse) and 10 healthy controls, with stool samples collected monthly for a year. Phageome profiling will be achieved via shotgun sequencing of phage genomes from the same stool samples. This dataset will be interrogated together with bacterial (16S rRNA) and fungal (ITS) amplicon data, which have just been generated. Available metadata include disease symptoms, diet, stress levels, work productivity, medication, and faecal calprotectin. Dynamic time-wrapping algorithms will be used to align time series of microbial members with similar temporal dynamics. Dynamic Bayesian Network modelling will infer interactions between microbiome members and predict future relapse.

Anticipated Impact

The phageome is the often neglected (“dark matter”) part of the microbiome, but has defining interactions with bacteria. We will expand knowledge on inter-species dynamics during relapse and remission cycles of UC. This will potentially lead to new microbiome-related relapse predictors, which may contribute to new prognostic tools in UC, and potentially inform therapeutic avenues.
Regularized regression can improve estimates of multivariate selection in the face of multicollinearity and limited data
Authors: Sztepanacz Jacqueline L , Houle David
Published: January 2024

The breeder’s equation, Δz¯=Gβ , allows us to understand how genetics (the genetic covariance matrix, G) and the vector of linear selection gradients β interact to generate evolutionary trajectories. Estimation of β using multiple regression of trait values on relative fitness revolutionized the way we study selection in laboratory and wild populations. However, multicollinearity, or correlation of predictors, can lead to very high variances of and covariances between elements of β, posing a challenge for the interpretation of the parameter estimates. This is particularly relevant in the era of big data, where the number of predictors may approach or exceed the number of observations. A common approach to multicollinear predictors is to discard some of them, thereby losing any information that might be gained from those traits. Using simulations, we show how, on the one hand, multicollinearity can result in inaccurate estimates of selection, and, on the other, how the removal of correlated phenotypes from the analyses can provide a misguided view of the targets of selection. We show that regularized regression, which places data-validated constraints on the magnitudes of individual elements of β, can produce more accurate estimates of the total strength and direction of multivariate selection in the presence of multicollinearity and limited data, and often has little cost when multicollinearity is low. We also compare standard and regularized regression estimates of selection in a reanalysis of three published case studies, showing that regularized regression can improve fitness predictions in independent data. Our results suggest that regularized regression is a valuable tool that can be used as an important complement to traditional least-squares estimates of selection. In some cases, its use can lead to improved predictions of individual fitness, and improved estimates of the total strength and direction of multivariate selection.
Forensic parasitology: a new frontier in criminalistics
Authors: Kwak Mackenzie L , Wallman James F , Yeo Darren , Archer Melanie S , Nakao Ryo
Published: January 2024

Parasites are ubiquitous, diverse, and have close interactions with humans and other animals. Despite this, they have not garnered significant interest from forensic scientists, and their utility as indicators in criminal investigations has been largely overlooked. To foster the development of forensic parasitology we explore the utility of parasites as forensic indicators in five broad areas: (i) wildlife trafficking and exploitation, (ii) biological attacks, (iii) sex crimes, (iv) criminal neglect of humans and other animals, and (v) indicators of movement and travel. To encourage the development and growth of forensic parasitology as a field, we lay out a four-step roadmap to increase the use and utility of parasites in criminal investigations.
Interferon Regulatory Factor 5 Regulates the Phagocytosis of Microglia and Alleviate Alzheimer’s Pathology
Authors: Fan Ziqi , Zhang Xinyi , Zhao Shuai , Zhong Siyan , Li Zheyu , Yan Yaping , Zhang Baorong , Chen Yanxing
Published: January 2024

Microglia play a critical role in the pathophysiology of Alzheimer’s disease. They are involved in Aβ-induced neuroinflammatory responses, regulating the production of inflammatory mediators. Interferon regulatory factor 5 (IRF5) plays a central role in inflammatory diseases in the periphery, the role of which in central nervous system remains elusive. This study aimed to investigate the role of IRF5 in Aβ-induced neuroinflammation and the progression of Aβ pathology. We found that Aβ1–42 oligomers significantly increased the level of IRF5 in BV2 microglia. The levels of proinflammatory cytokines TNF-α, IL-1β, and IL-6 were significantly upregulated with Aβ treatment. IRF5 knockdown with siRNA in microglia significantly reduced the expression of these proinflammatory factors induced by Aβ and promoted Aβ phagocytosis. Besides, LC3 upregulation and p62 downregulation were observed in IRF5 knockdown microglia. This was also validated in APP/PS1 mice with IRF5 knockdown, leading to reduced Aβ levels in the brain. We conclude that IRF5 mediates Aβ-induced microglial inflammatory responses. IRF5 knockdown attenuated Aβ-induced inflammatory responses and promoted the phagocytosis and autophagy of Aβ by microglia.
Usable Cybersecurity: a Contradiction in Terms?
Authors: Furnell Steven
Published: January 2024

Encounters and interactions with cybersecurity are now regular and routine experiences for information technology users across a variety of devices, systems and services. Unfortunately, however, despite long-term recognition of the importance of usability in the technology context, the user experience of cybersecurity and privacy is by no means guaranteed to address this criterion. This paper presents an outline of usability issues and challenges in the cybersecurity context, with examples of how it has (or indeed has not) evolved in some established contexts (looking in particular at web browsing and user authentication), as well as consideration of the extent to which any better attention is apparent within more recent and emerging technology contexts (considering the presentation of related features in scenarios including app stores and smart devices). Based on the evidence, cybersecurity is clearly yet to reach a stage where its mention would naturally imply usability, but at the same time the two concepts do not have to represent a contradiction in terms. The resulting requirement is for the increasing recognition of the issue to translate into a greater level of resulting attention and action.
Periventricular cyst as a complication of ventriculoperitoneal shunting in the context of intracranial haemorrhage: a case report and review of the literature
Authors: Smith Leon E , Zeman Brian D
Published: January 2024

Spontaneous intraventricular haemorrhage with hydrocephalus frequently requires neurosurgical intervention, including ventriculoperitoneal shunting. We describe a periventricular cyst following the placement of a ventriculoperitoneal shunt in a 67-year-old female patient. The patient was admitted for rehabilitation after a spontaneous left basal ganglia and diffuse intraventricular haemorrhage with hydrocephalus. Initial management included an extraventricular drain, followed by a ventriculoperitoneal shunt. On Day 5 of rehabilitation, the patient was urgently reviewed for reduced level of consciousness. A cerebrospinal fluid cyst was identified around the shunt catheter, with subacute haemorrhage within the cyst. The patient underwent a successful shunt revision, with rapid improvement in consciousness and resolution of the cyst. This case highlights the importance of pericatheter cyst as a differential diagnosis in patients with altered neurological status following ventriculoperitoneal shunting. Early detection and surgical revision can lead to rapid resolution of symptoms and a favourable prognosis.
Flexible sensors with zero Poisson's ratio
Authors: Huang Xin , Bu Tianzhao , Zheng Qingyang , Liu Shaoyu , Li Yangyang , Fang Han , Qiu Yuqi , Xie Bin , Yin Zhouping , Wu Hao
Published: January 2024

Flexible sensors have been developed for the perception of various stimuli. However, complex deformation, usually resulting from forces or strains from multi-axes, can be challenging to measure due to the lack of independent perception of multiaxial stimuli. Herein, flexible sensors based on the metamaterial membrane with zero Poisson's ratio (ZPR) are proposed to achieve independent detection of biaxial stimuli. By deliberately designing the geometric dimensions and arrangement parameters of elements, the Poisson's ratio of an elastomer membrane can be modulated from negative to positive, and the ZPR membrane can maintain a constant transverse dimension under longitudinal stimuli. Due to the accurate monitoring of grasping force by ZPR sensors that are insensitive to curvatures of contact surfaces, rigid robotic manipulators can be guided to safely grasp deformable objects. Meanwhile, the ZPR sensor can also precisely distinguish different states of manipulators. When ZPR sensors are attached to a thermal-actuation soft robot, they can accurately detect the moving distance and direction. This work presents a new strategy for independent biaxial stimuli perception through the design of mechanical metamaterials, and may inspire the future development of advanced flexible sensors for healthcare, human–machine interfaces and robotic tactile sensing.
Characteristics of Coronavirus Disease in Allogeneic Hematopoietic Stem Cell Transplantation During the Omicron Wave: A Single-Center Study
Authors: Zhu Panpan , Yang Luxin , Liu Lizhen , Lai Xiaoyu , Shi Jimin , Zhao Yanmin , Yu Jian , Fu Huarui , Ye Yishan , Wu Yibo , Huang He , Luo Yi
Published: January 2024

Objectives

This study aimed to characterize the clinical characteristics, outcomes, and risk factors for coronavirus disease 2019 (COVID-19) in 492 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) during the Omicron wave.

Methods

Data were retrospectively collected from patient charts and the electronic medical record systems at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2022 and January 2023.

Results

The median follow-up period of the entire cohort was 62 days. Myeloid malignancies (58.5%) and acute lymphocytic leukemia (30.5%) constituted the most common underlying disease. Among the 492 patients, 415, 67, and 10 exhibited mild, moderate, and severe COVID-19, respectively. The incidence of moderate-to-severe COVID-19 was 15.7%. The 60-day overall survival and complete resolution rates were 98.1% and 80.6%, respectively. The risk factors for moderate-to-severe COVID-19 included corticosteroid use within 3 months before diagnosis, <6 months interval between allo-HSCT and COVID-19 diagnosis, and antithymocyte globulin use for graft-versus-host disease prophylaxis.

Conclusions

During the Omicron wave, patients with allo-HSCT demonstrated a low COVID-19–related mortality rate and high moderate-to-severe and prolonged disease incidence. Prevention in the early posttransplantation period is critical for allo-HSCT recipients receiving corticosteroids.
Evidence evaluated by European Food Safety Authority does not support lowering the temporary tolerable daily intake for bisphenol A
Authors: Prueitt Robyn L , Goodman Julie E
Published: January 2024

The European Food Safety Authority (EFSA) recently derived a tolerable daily intake (TDI) for bisphenol A (BPA) of 0.2 ng/kg bw/day. There are several issues with EFSA’s hazard assessment review process, including that it was based on a limited subset of relevant studies. Multiple public commenters on EFSA’s draft evaluation of BPA, including several European regulatory agencies, noted these issues, yet they were not adequately addressed by EFSA in the final evaluation. The TDI for BPA was based on an intermediate immunotoxicity endpoint in mice that has not been observed in other species; there is no evidence that it is a precursor event to any downstream pathological outcome. The TDI is several orders of magnitude lower than estimates of safe doses of BPA established by agencies worldwide, including EFSA’s temporary TDI (t-TDI) for BPA established in 2015. Overall, the EFSA hazard assessment review process has led to a conclusion that there are low-dose effects of BPA based on very few, lower quality experimental animal studies. This conclusion is not supported by the totality of the available evidence, which includes multiple high-quality studies not considered by EFSA and indicates that the t-TDI established in 2015 is protective of human health.
Interleukin 28A aggravates Con A‐induced acute liver injury by promoting the recruitment of M1 macrophages
Authors: Zhang Junfeng , Cheng Dalei , Zhang Hui , Liu Zhihong , Gao Min , Wei Li , Yan Fenglian , Li Chunxia , Wang Lin , Dong Guanjun , Wang Changying , Zhao Mingsheng , Zhu Yuanbo , Xiong Huabao
Published: January 2024

Immune‐mediated acute hepatic injury is characterized by the destruction of a large number of hepatocytes and severe liver function damage. Interleukin‐28A (IL‐28A), a member of the IL‐10 family, is notable for its antiviral properties. However, despite advances in our understanding of IL‐28A, its role in immune‐mediated acute injury remains unclear. The present study investigated the role of IL‐28A in concanavalin A (Con A)‐induced acute immune liver injury. After Con A injection in mice, IL‐28A level significantly increased. IL‐28A deficiency was found to protect mice from acute liver injury, prolong survival time, and reduce serum aspartate aminotransferase and alanine aminotransferase levels. In contrast, recombinant IL‐28A aggravated liver injury in mice. The proportion of activated M1 macrophages was significantly lower in the IL‐28A‐deficiency group than in the wild‐type mouse group. In adoptive transfer experiments, M1 macrophages from WT could exacerbate mice acute liver injury symptoms in the IL‐28A deficiency group. Furthermore, the expression of proinflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), IL‐12, IL‐6, and IL‐1β, by M1 macrophages decreased significantly in the IL‐28A‐deficiency group. Western blotting demonstrated that IL‐28A deficiency could limit M1 macrophage polarization by modulating the nuclear factor (NF)‐κB, mitogen‐activated protein kinase (MAPK), and interferon regulatory factor (IRF) signaling pathways. In summary, IL‐28A deletion plays an important protective role in the Con A‐induced acute liver injury model and IL‐28A deficiency inhibits the activation of M1 macrophages by inhibiting the NF‐κB, MAPK, and IRF signaling pathways. These results provide a potential new target for the treatment of immune‐related hepatic injury.
Evidence for hypoxia‐induced dysregulated cholesterol homeostasis in preeclampsia: Insights into the mechanisms from human placental cells and tissues
Authors: Fuenzalida Barbara , Yañez Maria Jose , Mueller Martin , Mistry Hiten D. , Leiva Andrea , Albrecht Christiane
Published: January 2024

Preeclampsia (PE) poses a considerable risk to the long‐term cardiovascular health of both mothers and their offspring due to a hypoxic environment in the placenta leading to reduced fetal oxygen supply. Cholesterol is vital for fetal development by influencing placental function. Recent findings suggest an association between hypoxia, disturbed cholesterol homeostasis, and PE. This study investigates the influence of hypoxia on placental cholesterol homeostasis. Using primary human trophoblast cells and placentae from women with PE, various aspects of cholesterol homeostasis were examined under hypoxic and hypoxia/reoxygenation (H/R) conditions. Under hypoxia and H/R, intracellular total and non‐esterified cholesterol levels were significantly increased. This coincided with an upregulation of HMG‐CoA‐reductase and HMG‐CoA‐synthase (key genes regulating cholesterol biosynthesis), and a decrease in acetyl‐CoA‐acetyltransferase‐1 (ACAT1), which mediates cholesterol esterification. Hypoxia and H/R also increased the intracellular levels of reactive oxygen species and elevated the expression of hypoxia‐inducible factor (HIF)‐2α and sterol‐regulatory‐element‐binding‐protein (SREBP) transcription factors. Additionally, exposure of trophoblasts to hypoxia and H/R resulted in enhanced cholesterol efflux to maternal and fetal serum. This was accompanied by an increased expression of proteins involved in cholesterol transport such as the scavenger receptor class B type I (SR‐BI) and the ATP‐binding cassette transporter G1 (ABCG1). Despite these metabolic alterations, mitogen‐activated‐protein‐kinase (MAPK) signaling, a key regulator of cholesterol homeostasis, was largely unaffected. Our findings indicate dysregulation of cholesterol homeostasis at multiple metabolic points in both the trophoblast hypoxia model and placentae from women with PE. The increased cholesterol efflux and intracellular accumulation of non‐esterified cholesterol may have critical implications for both the mother and the fetus during pregnancy, potentially contributing to an elevated cardiovascular risk later in life.
Implementation and outcome of minimally invasive pancreatoduodenectomy in Europe: a registry-based retrospective study – a critical appraisal of the first 3 years of the E-MIPS registry
Authors: Emmen Anouk M.L.H. , de Graaf Nine , Khatkov I.E. , Busch O.R. , Dokmak S. , Boggi Ugo , Groot Koerkamp Bas , Ferrari Giovanni , Molenaar I.Q. , Saint-Marc Olivier , Ramera Marco , Lips Daan J. , Mieog J.S.D. , Luyer Misha D.P. , Keck Tobias , D’Hondt Mathieu , Souche F.R. , Edwin Bjørn , Hackert Thilo , Liem M.S.L. , Iben-Khayat Abdallah , van Santvoort H.C. , Mazzola Michele , de Wilde Roeland F. , Kauffmann E.F. , Aussilhou Beatrice , Festen Sebastiaan , Izrailov R. , Tyutyunnik P. , Besselink M.G. , Abu Hilal Mohammad ,   for the European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS)
Published: January 2024

Background:

International multicenter audit-based studies focusing on the outcome of minimally invasive pancreatoduodenectomy (MIPD) are lacking. The European Registry for Minimally Invasive Pancreatic Surgery (E-MIPS) is the E-AHPBA endorsed registry aimed to monitor and safeguard the introduction of MIPD in Europe.

Materials and Methods:

A planned analysis of outcomes among consecutive patients after MIPD from 45 centers in 14 European countries in the E-MIPS registry (2019–2021). The main outcomes of interest were major morbidity (Clavien–Dindo grade ≥3) and 30-day/in-hospital mortality.

Results:

Overall, 1336 patients after MIPD were included [835 robot-assisted (R-MIPD) and 501 laparoscopic MIPD (L-MIPD)]. Overall, 20 centers performed R-MIPD, 15 centers L-MIPD, and 10 centers both. Between 2019 and 2021, the rate of centers performing L-MIPD decreased from 46.9 to 25%, whereas for R-MIPD this increased from 46.9 to 65.6%. Overall, the rate of major morbidity was 41.2%, 30-day/in-hospital mortality 4.5%, conversion rate 9.7%, postoperative pancreatic fistula grade B/C 22.7%, and postpancreatectomy hemorrhage grade B/C 10.8%. Median length of hospital stay was 12 days (IQR 8–21). A lower rate of major morbidity, postoperative pancreatic fistula grade B/C, postpancreatectomy hemorrhage grade B/C, delayed gastric emptying grade B/C, percutaneous drainage, and readmission was found after L-MIPD. The number of centers meeting the Miami Guidelines volume cut-off of ≥20 MIPDs annually increased from 9 (28.1%) in 2019 to 12 (37.5%) in 2021 (P=0.424). Rates of conversion (7.4 vs. 14.8% P<0.001) and reoperation (8.9 vs. 15.1% P<0.001) were lower in centers, which fulfilled the Miami volume cut-off.

Conclusion:

During the first 3 years of the pan-European E-MIPS registry, morbidity and mortality rates after MIPD were acceptable. A shift is ongoing from L-MIPD to R-MIPD. Variations in outcomes between the two minimally invasive approaches and the impact of the volume cut-off should be further evaluated over a longer time period.
Racial inequities in HIV incidence among men who have sex with men prior to and amidst an Ending the HIV Epidemic initiative
Authors: Jamison Kelly E. , Braunstein Sarah L. , Pathela Preeti
Published: January 2024

Objective:

The aim of this study was to examine trends in HIV incidence among men who have sex with men (MSM) relative to the scale up of Ending the HIV Epidemic (EHE) initiatives, including biomedical prevention strategies, and to describe racial inequities over time.

Design:

A cross-sectional study, matching annual cohorts of New York City (NYC) Sexual Health Clinic (SHC) patients from 2010 to 2018 to the citywide HIV registry to identify seroconversions during 1 year of follow-up, through 2019.

Methods:

We examined HIV incidence for each annual cohort of MSM using diagnoses within 1 year after last negative HIV test. We calculated incidence rates and rate ratios (IRR) pooled across 3-year intervals (2010–2012, 2013–2015, 2016–2018) by race/ethnicity, age, neighborhood poverty level, recent STI diagnosis, and condom use during anal sex.

Results:

There were 36 156 study visits among MSM attending NYC SHCs, including 37% among White MSM and 63% among MSM of color. From 2010 to 2018, HIV incidence decreased overall from 2.82 to 0.82/100 person-years, and among all race/ethnicity, age, poverty, STI, and condom use subgroups. For 2010–2012 vs. 2016–2018, adjusted IRRs (95% CI) increased for Black MSM [1.8 (1.3–2.6) vs. 6.0 (3.5–10.2)], Latino MSM [1.4 (1.0–2.0) vs. 4.0 (2.3–6.8)], and MSM of other races [1.0 (0.6–1.7) vs. 2.5 (1.3–4.9)] compared with White MSM. Black and Latino MSM seroconverted at significantly higher rates than White MSM in the same age groups and neighborhood poverty level.

Conclusion:

Despite decreases in HIV incidence among MSM, racial inequities were exacerbated over time. Addressing structural factors that impact racial inequities in risk of HIV should undergird EHE initiatives.
Association Between Anesthesiologist Sex and Patients’ Postoperative Outcomes: A Population-based Cohort Study
Authors: Jerath Angela , Satkunasivam Raj , Kaneshwaran Kirusanthy , Aminoltejari Khatereh , Chang Ashton , MacDonell D. Su-Yin , Kealey Alayne , Ladowski Stephanie , Sarmah Anita , Flexman Alana M. , Lorello Gianni R. , Nabecker Sabine , Coburn Natalie , Conn Lesley Gotlib , Klaassen Zachary , Ranganathan Sanjana , Riveros Carlos , McCartney Colin J.L. , Detsky Allan S. , Wallis Christopher J.D.
Published: January 2024

Objective:

To examine the association of anesthesiologist sex on postoperative outcomes.

Summary Background Data:

Differences in patient postoperative outcomes exist, depending on whether the primary surgeon is male or female, with better outcomes seen among patients treated by female surgeons. Whether the intraoperative anesthesiologist’s sex is associated with differential postoperative patient outcomes is unknown.

Methods:

We performed a population-based, retrospective cohort study among adult patients undergoing one of 25 common elective or emergent surgical procedures from 2007–2019 in Ontario, Canada. We assessed the association between sex of the intraoperative anesthesiologist and the primary endpoint of adverse postoperative outcome, defined as death, readmission, or complication within 30-days following surgery using generalized estimating equations.

Results:

Among 1,165,711 patients treated by 3,006 surgeons and 1,477 anesthesiologists, 311,822 (26.7%) received care from a female anesthesiologist and 853,889 (73.3%) from a male anesthesiologist. Overall, 10.8% of patients experienced one or more adverse postoperative outcomes of whom 1.1% died. Multivariable adjusted rates of the composite primary endpoint were higher among patients treated by male anesthesiologists (10.6%) compared to female anesthesiologists (10.4%; adjusted odds ratio 1.02, 95% CI 1.00-1.05, P=0.048).

Conclusions:

We demonstrated a significant association between sex of the intraoperative anesthesiologist and patient short-term outcomes after surgery in a large cohort study. This study supports growing literature of improved patient outcomes among female practitioners. The underlying mechanisms of why outcomes differ between male and female physicians remain elusive and require further in-depth study.
Phenotypic and genotypic characterization of Marinobacterium weihaiense sp. nov. and Marinobacterium marinum sp. nov., isolated from marine sediment, and genomic properties of the genus Marinobacterium
Authors: Liu Xin-Jiang , Zhu Ke-Lei , Ye Yu-Qi , Han Ze-Tian , Tan Xin-Yun , Du Zong-Jun , Ye Meng-Qi
Published: January 2024

In this study, two novel bacterial strains were isolated from coastal sediment of Weihai, China. The two strains were Gram-stain-negative and facultatively aerobic, designated 3-1745T and A346T. Based on phenotypic, genetic and phylogenetic properties, strains 3-1745T and A346T represent two novel species of the genus

Marinobacterium

. The results of genome analysis revealed many central carbohydrate metabolism pathways such as gluconeogenesis, pyruvate oxidation, tricyclic acid cycle, pentose phosphate pathway and PRPP biosynthesis in the genus

Marinobacterium

. The ability of strains 3-1745T and A346T to utilize volatile fatty acids was experimentally confirmed. Polyhydroxyalkanoate synthases (PhaA, PhaB and PhaC) for the synthesis of polyhydroxyalkanoates were prevalent in the genus

Marinobacterium

. Multiple BGCs (biosynthetic gene clusters) including betalactone, ectoine, ranthipeptide, redox-cofactor, RiPPs (ribosomally synthesized post-translationally modified peptides) and T3PKS (polyketide synthases) in the genome of the genus

Marinobacterium

were found. Additional genome analyses suggested that the genus

Marinobacterium

contained diverse potential mechanisms of salt tolerance and mainly utilized oligosaccharides. This is the first report on broad genomic analyses of the genus

Marinobacterium

with the description of two novel species and potential ecological and biotechnological implications.
Nano Colonies: Rearing honey bee queens and their offspring in small laboratory arenas
Authors: Lamas Zachary S. , Solmaz Serhat , Stevens Cory , Bragg Jason , Ryabov Eugene V. , Madella Shayne , Corona Miguel , Evans Jay D.
Published: January 2024

Honey bees create complex societies of self-organized individuals in intricate colonies. Studies of honey bees are carried out in both the field and the laboratory. However, field research is encumbered by the difficulties of making reliable observations and environmental confounders. Meanwhile, laboratory trials produce data that are not field realistic as they lack key characteristics of a natural colony. Additionally, advances in honey bee research have been hindered without reliable methodology to rear queens in the laboratory. Here we provide a new system to reliably produce queens and worker brood in the laboratory and describe how this system fits with artificial insemination of queens as a step towards a continuous self-contained source of bees. The process creates a bridge between field research and laboratory trials and provides a secure system for contagious or regulated elements while maintaining many of the intrinsic characteristics of a honey bee colony.
DiffModeler: Large Macromolecular Structure Modeling in Low-Resolution Cryo-EM Maps Using Diffusion Model
Authors: Wang Xiao , Zhu Han , Terashi Genki , Taluja Manav , Kihara Daisuke
Published: January 2024

Cryogenic electron microscopy (cryo-EM) has now been widely used for determining multi-chain protein complexes. However, modeling a complex structure is challenging particularly when the map resolution is low, typically in the intermediate resolution range of 5 to 10 Å. Within this resolution range, even accurate structure fitting is difficult, let alone de novo modeling. To address this challenge, here we present DiffModeler, a fully automated method for modeling protein complex structures. DiffModeler employs a diffusion model for backbone tracing and integrates AlphaFold2-predicted single-chain structures for structure fitting. Extensive testing on cryo-EM maps at intermediate resolutions demonstrates the exceptional accuracy of DiffModeler in structure modeling, achieving an average TM-Score of 0.92, surpassing existing methodologies significantly. Notably, DiffModeler successfully modeled a protein complex composed of 47 chains and 13,462 residues, achieving a high TM-Score of 0.94. Further benchmarking at low resolutions (10-20 Å) confirms its versatility, demonstrating plausible performance. Moreover, when coupled with CryoREAD, DiffModeler excels in constructing protein-DNA/RNA complex structures for near-atomic resolution maps (0-5 Å), showcasing state-of-the-art performance with average TM-Scores of 0.88 and 0.91 across two datasets.
An active light signalling pathway is necessary for ABA-induced inhibition of hypocotyl elongation
Authors: Cañibano Esther , Soto-Gomez Daniela , Oliveros Juan Carlos , Bourbousse Clara , Fonseca Sandra
Published: January 2024

Driven by cell elongation, hypocotyl growth is tightly controlled by light and responds to external stimuli and endogenous hormonal pathways. Hypocotyls are known to be responsive to the stress signalling hormone abscisic acid (ABA) which effectively inhibits cell elongation, but how this regulation is connected to light responses and other endogenous hormonal pathways has been a subject of limited studies. Here, we show that whereas hypocotyl elongation is sensitive to ABA in light-grown seedlings, the hypocotyl of dark-grown etiolated seedlings is ABA-insensitive. In the dark, hypocotyl sensitivity to ABA is restored in the constitutive photomorphogenicpifqandcop1-4mutants, suggesting that an active light signalling pathway is necessary for hypocotyl responsiveness to ABA. However, etiolated hypocotyls retain ABA responsiveness, as could be detected by the induction ofABI1andRD29Btranscripts in response to exogenous ABA, suggesting that inhibition of hypocotyl elongation mediated by ABA does not follows the canonical ABA signalling dependent on transcription. Here, using RNA-seq analysis we identified a number of ABA differentially expressed genes (DEGs) that correlate with ABA inhibition of hypocotyl elongation, specifically in dark-grownpifqor light-grown WT plants, and whose expression remains unchanged by ABA treatment in dark-grown WT plants. Among these DEGs we identified a number of genes playing a role in cell elongation directly at the level of the plasma membrane, as SAURs, ion transporters, auxin flux regulators, channels, and cell wall modification enzymes. The use of the auxin transport inhibitor, NPA, revealed that in the light auxin transport impairment renders hypocotyls insensitive to ABA in WT andpifqplants. Thus, in the light, hypocotyl responsiveness to ABA is dependent on auxin transport and independent of PIFs. In the dark, PIFs render hypocotyls insensitive to ABA, perhaps by regulating the expression of a number of ABA DEGs, a mechanism that could allow plants to prioritize the elongation towards light, avoiding to slow-down soil emergence that could be induced by ABA signalling in case of sudden reduction of soil moisture.
Can overlooking ‘invisible landscapes’ bias habitat selection estimation and population distribution projections?
Authors: Dejeante Romain , Lemaire-Patin Rémi , Chamaillé-Jammes Simon
Published: January 2024

Species’ future distributions are commonly predicted using models that link the likelihood of occurrence of individuals to the environment. Although animals’ movements are influenced by physical landscapes and individual experiences (for example space familiarity), species distribution models developed from observations of unknown individuals cannot integrate these latter variables, turning them into ‘invisible landscapes’. In this theoretical study, we address how overlooking ‘invisible landscapes’ impacts the estimation of habitat selection and thereby the projection of future distributions. Overlooking the attraction towards some ‘invisible’ variable consistently led to over-estimating the strength of habitat selection. Consequently, projections of future population distributions were also biased, with animals tracking habitat changes less than predicted. Our results reveal an overlooked challenge faced by correlative species distribution models based on the observation of unknown individuals, whose past experience of the environment is by definition not known. Mechanistic distribution modelling integrating cognitive processes underlying movement should be developed.
Provisioning polyethylene glycol (PEG) to large herbivores in nutrient poor savannas can break food limitation
Authors: Schroder Bradley , Van Langevelde Frank , Schroder Nicola-Anne Hawkins , Prins Herbert H. T.
Published: January 2024

Reproduction and survival of herbivores in nutrient poor savannas is low due to low nutrient and energy availability, partly caused by high levels of tannins. Polyethylene glycol (PEG) increases the availability of proteins for herbivores by binding tannins. The effect of PEG on the diet of free-roaming herbivores has not been tested. Our hypothesis was deploying lick blocks with the addition of PEG in a nutrient poor savanna, will result in a broadening of the diet of free-roaming herbivores with higher percentages of browse species and higher utilisation per browse species, with higher tannin levels. We further hypothesised that the mineral content in the faeces, once exposed to PEG would increase. We collected faecal samples of five herbivore species with various feeding methods (grazers, browsers or mixed feeders). The study used a Before-After-Control-Impact (BACI) design. The results show that the addition of PEG promotes a change in the browse dietary choices of four of the five herbivore species, and are expressed as a broader choice of diet, coupled with higher numbers of browse species with low edibility and higher tannin levels. The addition of PEG had no noteworthy effect on the concentration of minerals found in the faeces.
Gene expression tradeoffs determine bacterial survival and adaptation to antibiotic stress
Authors: Kratz Josiah C. , Banerjee Shiladitya
Published: January 2024

To optimize their fitness, cells face the crucial task of efficiently responding to various stresses. This necessitates striking a balance between conserving resources for survival and allocating resources for growth and division. The fundamental principles governing these tradeoffs is an outstanding challenge in the physics of living systems. In this study, we introduce a coarse-grained theoretical framework for bacterial physiology that establishes a connection between the physiological state of cells and their survival outcomes in dynamic environments, particularly in the context of antibiotic exposure. Predicting bacterial survival responses to varying antibiotic doses proves challenging due to the profound influence of the physiological state on critical parameters, such as the Minimum Inhibitory Concentration (MIC) and killing rates, even within an isogenic cell population. Our proposed theoretical model bridges the gap by linking extracellular antibiotic concentration and nutrient quality to intracellular damage accumulation and gene expression. This framework allows us to predict and explain the control of cellular growth rate, death rate, MIC and survival fraction in a wide range of time-varying environments. Surprisingly, our model reveals that cell death is rarely due to antibiotic levels being above the maximum physiological limit, but instead survival is limited by the inability to alter gene expression sufficiently quickly to transition to a less susceptible physiological state. Moreover, bacteria tend to overexpress stress response genes at the expense of reduced growth, conferring greater protection against further antibiotic exposure. This strategy is in contrast to those employed in different nutrient environments, in which bacteria allocate resources to maximize growth rate. This highlights an important tradeoff between the cellular capacity for growth and the ability to survive antibiotic exposure.
Studying self-assembly of norovirus capsid by a combination ofin silicomethods
Authors: Carvaillo Jean-Charles , Tubiana Thibault , Detchanamourtty Sella , Bressanelli Stéphane , Barroso da Silva Fernando Luís , Boulard Yves
Published: January 2024

Understanding how macromolecular assembly occurs is a fundamental and challenging problem because spontaneous, precise assembly is at the center of most biological processes. It is an elaborate process that requires non-covalent stable interactions between partners to stabilize the desired architecture for a specific purpose. One of the advantages of virus models is that under adequate conditions capsid proteins can be efficiently assembledin vitroin the absence of any other component, providing simplified experimental models that can be rigorously characterized. The present study aims at describing the initial steps of molecular self-assembly of norovirus-like particles (NoVLPs, composed solely of the major norovirus capsid protein VP1), by combiningin silicocomputational approaches to explore complementary physical properties. We show that this strategy allows not only recapitulating but also revising a former NoVLP assembly model. Our approach can be applied and extended to other problems in macromolecular assembly.
Unravelling Different Biological Roles Of Plant Synaptotagmins
Authors: García-Hernández Selene , Rubio Lourdes , Pérez-Sancho Jessica , Esteban del Valle Alicia , Benítez-Fuente Francisco , Beuzón Carmen R. , Macho Alberto P. , Ruiz-López Noemi , Albert Armando , Botella Miguel A.
Published: January 2024

Endoplasmic Reticulum-Plasma Membrane contact sites (ER-PM CS) are evolutionarily conserved membrane domains found in all eukaryotes, where the endoplasmic reticulum (ER) closely interfaces with the plasma membrane (PM). This short distance, typically 10-30 nm, is achieved in Arabidopsis through the action of tether proteins such as Synaptotagmins (SYTs). Arabidopsis comprises five SYT members (SYT1-SYT5), but whether they possess overlapping or distinct biological functions remains elusive.SYT1is the best-characterized gene member and plays an essential role in the resistance to abiotic stress. This study reveals that while the functionally redundantSYT1andSYT3genes are involved in salt and cold stress resistance,SYT5is associated withPseudomonas syringaeresistance despite evidence ofin vivointeraction between SYT1 and SYT5. Structural phylogenetic analysis indicates that SYT1 and SYT5 clades emerged early in the evolution of land plants. These protein clades exhibit different structural features, rationalizing their distinct biological roles.