bluuebunny/crossref_metadata_2025 huggingface dataset:
eBiBa: A Post-Quantum Hash-Based Signature With Small Signature Size in the Continuous Communication of Large-Scale Data
Authors: Li Lingyun , Lu Xianhui , Wang Kunpeng
Published: July 2023

We present eBiBa (enhanced BiBa), a hash-based signature scheme with the smallest possible signature size, while ensuring high feasibility and security in a specific application model. Our scheme is tailored to address the communication requirement of a large-scale public data stream continuously disseminated between two participants while ensuring data source and data integrity authentication. To achieve these goals, firstly, we optimized the classical hash tree mode into a hybrid mode to efficiently perform public key authentication and eliminate the need for an authenticated channel to transmit large amounts of data, unlike the initial BiBa-based broadcast authentication protocol. Secondly, we employed a specific tweakable hash chain function to digest a batch of messages, reducing the required conditions for post-quantum existential unforgeability under adaptive chosen message attack (EUCMA) of eBiBa to a second-pre-image-resistance-like property instead of collision resistance. This results in reduced pre-computation in both key and signature generations. Thirdly, we utilized a forward-secure pseudorandom function to achieve forward-secure of the proposed scheme. Finally, we minimize the signature size through a series of procedures. Firstly, we select BiBa few-time signature as the underlying signature scheme since it is currently the few-time hash-based signature with the smallest signature size that we are aware of; in addition, the hybrid approach we employed can also significantly reduce the signature size compared to using a hash tree solely; for the hash tree structure, we design a specific authentication path in combination with the related communication model to further minimize the signature size; finally, we optimize the authentication approach to achieve the minimum signature size in a single transmission. Our construction minimizes the signature size in the aforementioned model, achieving a compression rate of 0.017 to 0.828 based on distinct values of parameters, as compared to XMSS-256. We also demonstrated that eBiBa can achieve post-quantum forward-secure and EUCMA security.
Farmers’ acceptance of the income stabilisation tool: a discrete choice experiment application
Authors: Čop Tajana , Cerroni Simone , Njavro Mario
Published: July 2023

The income stabilisation tool (IST) is the latest tool proposed by the European Union (EU) to manage agricultural risks. It aims at stabilising farm income by compensating income losses. Using a discrete choice experiment, this paper investigates grapevine farmers’ acceptance of the IST in Croatia and tests whether behavioural factors such as risk preferences, probability weighting and subjective probabilities related to future farm income explain acceptance of this new tool. Results suggest that there is demand for the IST. Pessimistic farmers are more likely to participate in the IST than others, suggesting that subjective probabilities influence farmers’ decisions about agricultural risk management.
Left ventricular assist device explantation using a new double-patch technique
Authors: Bhadra Oliver Daniel , Pausch Jonas , Aubin Hug , Akhyari Payam , Lichtenberg Artur , Barten Markus Johannes , Alassar Yousuf , Reichenspurner Hermann , Bernhardt Alexander Markus
Published: July 2023

OBJECTIVES

There are several surgical approaches for explanting a left ventricular assist device (LVAD) after recovery of cardiac function. Thus, remaining ventricular assist device components may bear significant risks of infection or thrombosis. We hereby report our technique and two-center experience with explantation of LVADs using a new double-patch technique.

METHODS

From March 2019 to April 2021, five patients underwent LVAD explantation after myocardial recovery (HVAD, n = 2; HeartMate 3, n = 3). The mean patient age was 50.3 years (100% male); the mean time on the LVAD was 23.1 ± 20.8 months. The aetiology of the primary heart failure was dilated cardiomyopathy (n = 4) and myocarditis (n = 1).

LVAD explantation was performed using a median sternotomy and cardiopulmonary bypass. The LVAD was stopped, and the outflow graft was clamped. The outflow graft was ligated and sutured close to the aortic anastomosis. The driveline was clipped and removed. Under induced fibrillation, the attachment of the LVAD was released from the apical cuff and the LVAD was removed. A round pericardial patch was fixed from the inner of the ventricle. This step sealed the apex of the heart. An additional Gore-Tex patch was continuously sutured epicardially over the suture ring.

RESULTS

The 5 cases showed technically uncomplicated explantation of the LVADs. During the follow-up of a mean of 16.4 ± 16.9 months, we observed 100% survival. There were no bleeding complications or thromboembolic events during the follow-up period.

CONCLUSIONS

LVAD explantation with the double-patch technique is feasible and safe. This technique allows discontinuation of anticoagulation. The 30-day survival was 100%. Further studies are needed to provide better evidence for LVAD explantation and long-term follow-up.
Cyber and AI security challenges for LNG maritime transport and terminals—responses in law and standards
Authors: Jao Juei-Cheng , Chuah Jason C T
Published: July 2023

This article considers how key state players in the maritime transport and storage of liquefied natural gas (LNG) face up to the cyber security threats which have sadly become ubiquitous in recent times. The cyber threat for the gas sector, with increasing investment in LNG and current geopolitics, makes the study especially acute.
Targeted RNA condensation in living cells via genetically encodable triplet repeat tags
Authors: Xue Zhaolin , Ren Kewei , Wu Rigumula , Sun Zhining , Zheng Ru , Tian Qian , Ali Ahsan Ausaf , Mi Lan , You Mingxu
Published: July 2023

Living systems contain various membraneless organelles that segregate proteins and RNAs via liquid–liquid phase separation. Inspired by nature, many protein-based synthetic compartments have been engineered in vitro and in living cells. Here, we introduce a genetically encoded CAG-repeat RNA tag to reprogram cellular condensate formation and recruit various non-phase-transition RNAs for cellular modulation. With the help of fluorogenic RNA aptamers, we have systematically studied the formation dynamics, spatial distributions, sizes and densities of these cellular RNA condensates. The cis- and trans-regulation functions of these CAG-repeat tags in cellular RNA localization, life time, RNA–protein interactions and gene expression have also been investigated. Considering the importance of RNA condensation in health and disease, we expect that these genetically encodable modular and self-assembled tags can be widely used for chemical biology and synthetic biology studies.
Antibody responses following the surge of SARS-CoV-2 Omicron infection among patients with systemic autoimmune rheumatic diseases
Authors: Xiang Nan , Li Yu-Jing , Liu Meng-Yao , Wu Qi-Qin , Zhang Ya-Xin , Jin Hui-Zhi , Wang Qian , Li Yu-Wei , Tong Da-Li , Xue Tian , Jin Teng-Chuan , Bao Wei , Chen Zhu
Published: July 2023

Objectives

The surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron infections has affected most Chinese residents at the end of 2022, including a number of patients with systemic autoimmune rheumatic diseases (SARDs).

Methods

To investigate the antibody level of the Omicron variant in SARD patients after SARS-CoV-2 Omicron infection, we tested BA.5.2 and BF.7 Omicron variant IgG antibody levels using ELISA on blood samples collected from 102 SARD patients and 19 healthy controls (HCs). The type of SARD, demographics, concurrent treatment, doses of SARS-CoV-2 vaccines and outcomes were also recorded.

Results

A total of 102 SARD patients (mean age: 40.3 years; 89.2% female), including 60 SLE, 32 RA and 10 other SARDs, were identified. Of these, 87 (85.3%) were infected with SARS-CoV-2. We found that the BA.5.2 and BF.7 antibody levels of infected SARD patients were lower than those of HCs (P < 0.05). Sixty-five (63.7%) patients had at least one dose of a SARS-CoV-2 vaccine. SARD patients with at least two doses of SARS-CoV-2 vaccine had a higher level of BA.5.2 and BF.7 antibodies than the unvaccinated group (P < 0.05). There was no evidence for a significant inhibitory effect of glucocorticoids (GCs) on the BA.5.2 and BF.7 Omicron variant antibody levels in SARD patients. SLE patients using biologic DMARDs had a lower BA.5.2 Omicron variant antibody level than patients using GCs and/or HCQ.

Conclusion

These data suggest that patients with SARDs had a lower antibody response than HCs after Omicron infection.
Fungicide Use Patterns in Select United States Wine Grape Production Regions
Authors: Oliver Charlotte , Cooper Monica , Ivey Melanie Lewis , Brannen Phillip , Miles Timothy , Lowder Sarah , Mahaffee Walter , Moyer Michelle M.
Published: July 2023

Wine grape production (Vitis sp.) in the United States requires fungicide inputs for disease control. Currently, there is limited data available on vineyard fungicide use patterns. This information is important in developing tailored recommendations for disease management and fungicide stewardship. In this paper, we summarize the wine grape vineyard fungicide use patterns from four major regions: Napa and Sonoma valleys (California), Willamette Valley (Oregon), Columbia Valley (Washington), and several smaller regions east of the Mississippi River in years 2009 to 2020. We learned that the average in-season total fungicide applications ranged regionally from 5.6 to 8. The most commonly applied Fungicide Resistance Action Committee (FRAC) codes in spray programs were FRAC 3, 13, and M02 across all regions, with some variation to the top four groups in each region. Most applications were made on 14-day intervals; however, shorter intervals (7-day) were favored early season, and longer intervals (21-day) were favored late season. Tank-mixing multiple active ingredients was common east of the Mississippi River during all stages of grape development; this action was typically favored during the bloom period in other regions. In a subset of records that participated in FRAC 11 fungicide resistance testing, the average number of FRAC 11 applications after testing was reduced to either no applications or one application in Napa and Sonoma valleys. This survey provides regionally specific data related to fungicide stewardship practices that could be a focus for future stewardship messaging and fungicide resistance selection training, including total product use (selection events), spray intervals (selection pressure), and tank mixing (selection management).

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
A Reevaluation of Phylogenomic Data Reveals that Current Understanding in Wheat Blast Population Biology and Epidemiology Is Obfuscated by Oversights in Population Sampling
Authors: Farman Mark L. , Ascari Joao P. , Rahnama Mostafa , Ponte Emerson M. Del , Pedley Kerry F. , Martinez Sebastián , Fernandes José Maurício C. , Valent Barbara
Published: July 2023

Wheat blast, caused by the Pyricularia oryzae Triticum lineage (PoT), first emerged in Brazil and quickly spread to neighboring countries. Its recent appearance in Bangladesh and Zambia highlights a need to understand the disease's population biology and epidemiology so as to mitigate pandemic outbreaks. Current knowledge is mostly based on characterizations of Brazilian wheat blast isolates and comparison with isolates from non-wheat, endemic grasses. These foregoing studies concluded that the wheat blast population lacks host specificity and, as a result, undergoes extensive gene flow with populations infecting non-wheat hosts. Additionally, based on genetic similarity between wheat blast and isolates infecting Urochloa species, it was proposed that the disease originally emerged via a host jump from this grass and that Urochloa likely plays a central role in wheat blast epidemiology owing to its widespread use as a pasture grass. However, due to inconsistencies with broader phylogenetic studies, we suspected that these seminal studies had not actually sampled the populations normally found on endemic grasses and, instead, had repeatedly isolated members of PoT and the related Lolium pathogen lineage (PoL1). Re-analysis of the Brazilian data as part of a comprehensive, global, phylogenomic dataset that included a small number of South American isolates sampled away from wheat confirmed our suspicion and identified four new P. oryzae lineages on grass hosts. As a result, the conclusions underpinning current understanding in wheat blast's evolution, population biology, and epidemiology are unsubstantiated and could be equivocal.
‘Candidatus Liberibacter asiaticus’ Expands and Scavenges the Nutritional Choline Pool in Its Host Grapefruit (Citrus × paradisi) Leaves
Authors: Jain Mukesh , Cai Lulu , Gabriel Dean W.
Published: July 2023

Phosphatidylcholine (PtdCho) is an unusual membrane phospholipid present in some endosymbiotic and intracellular pathogenic prokaryotes. ‘ Candidatus Liberibacter asiaticus’ (CLas) is a phloem-limited, uncultured, fastidious α-Proteobacterium associated with the devastating citrus “greening” disease (huanglongbing). Phylogenetically related but nonpathogenic Liberibacter crescens (Lcr) was used as a culturable surrogate to examine PtdCho biosynthesis in pathogenic CLas. Genes encoding key enzymes for two alternative PtdCho biosynthetic routes are present in the Lcr genome: the one-step cytidine diphosphate (CDP)-choline ( pcs-encoding phosphatidylcholine synthase) and the three-step methyl-transferase pathway ( pmt-encoding phospholipid N-methyltransferase). However, only the CDP-choline pathway genes for incorporating exogenous Cho were identified in the CLas genome. Exogenous Cho enhanced growth and alleviated osmotic stress in wild-type Lcr and in the pmt insertion mutant strains when cultured in a sugar-rich medium. Quantitative RT-PCR analyses confirmed active uptake and condensation of nutritional Cho into PtdCho by CLas in both its plant host and psyllid vector. CLas-infected grapefruit leaves showed transcriptional activation of Cho biosynthesis genes and 2.8-fold higher levels of Cho. In plant cells, the compatible osmolyte glycine-betaine (GlyBet) is also derived from Cho. Expression of GlyBet biosynthesis genes and the GlyBet content were similar in both CLas-infected and healthy leaf tissue. The data presented here suggest that CLas likely exploits the Cho biosynthetic pathway in citrus hosts to expand the nutritional Cho pool.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Patient Experience and Clinical Outcomes after Same-day Outpatient Mastectomy and Immediate Breast Reconstruction Protocol during the Global Pandemic
Authors: Mohan Anita T. , MacArthur Taleen A. , Murphy Brenna , Song Allisa J. , Saifuddin Hiba , Degnim Amy , Harmsen William S. , Martinez-Jorge Jorys , Jakub James W. , Vijayasekaran Aparna
Published: July 2023

Background:

The coronavirus disease 2019 (COVID-19) pandemic provoked rapid changes in clinical practice to accommodate mandated restrictions within healthcare delivery. This study reviewed patient-reported experiences and clinical outcomes after implementation of a same-day discharge protocol after mastectomy with immediate alloplastic breast reconstruction compared with our historical overnight stay protocol.

Methods:

This is a retrospective single-institution study of consecutive patients who underwent mastectomy and immediate alloplastic reconstruction between July 2019 and November 2020. A postoperative survey was completed by patients to evaluate satisfaction with perioperative communications, recovery, and their overall experience.

Results:

A total of 302 patients (100% women) underwent mastectomy and immediate alloplastic reconstruction (174 pre-COVID-19, 128 during COVID-19). During COVID-19, 71% of patients were scheduled for a same-day discharge, among which 89% were successfully discharged the same day. Compared with pre-COVID-19, there were no differences in type of surgery, operative times, pain scores, 30-day readmission, or unplanned visits (allP> 0.05) during the COVID-19 pandemic. Compared with pre-COVID-19, patients during the pandemic reported comparable satisfaction with their care experience and postoperative recovery (56% survey response rate). Patient satisfaction was also similar between those discharged the same day (n = 81) versus the next day (n = 47) during COVID-19.

Conclusions:

Same-day discharge is feasible, safe, and can provide similar patient-reported satisfaction and outcomes compared with traditional overnight stay. These data highlight the ability to deliver adaptable, high-quality breast cancer care, within the constraints of a global pandemic.
Eccrine Ductal Carcinoma of the Eyelid
Authors: Casale Jarett J. , Uddin Sabiha B. , Proia Alan D.
Published: July 2023

The authors present the third example of an eccrine ductal carcinoma of the eyelid. A woman in her early 70s presented with a lesion of the central right lower eyelid margin in the vicinity where an actinic keratosis was diagnosed by biopsy 2.75 years previously. Her dermatologist and ophthalmologist monitored the area of actinic keratosis, and it was stable for 2.5 years until the area became ulcerated and thickened with the loss of eyelashes. A wedge resection disclosed a squamous cell carcinoma in situ and a separate eccrine ductal carcinoma. The eccrine ductal carcinoma had in situ tumor thickening, an eccrine duct component, and an invasive tumor infiltrating the tarsal plate and replacing the normal meibomian glands. The invasive eccrine ductal carcinoma only mildly thickened the tarsal plate and was most likely an incidental finding in a biopsy prompted by the squamous cell carcinoma in situ. The 5-year relative survival rate for malignant apocrine-eccrine tumors is approximately 97%, and our patient is alive and without evidence of local or distant tumor recurrence 5.5 years following the excision of her eyelid tumor.
Increasing depth of focus with allogeneic presbyopic inlays: 3-year results
Authors: Keskin Perk Fatma Feyza Nur , Taneri Suphi , Tanriverdi Cafer , Haciagaoglu Sezer , Karaca Zeki Yigit , Kilic Aylin
Published: July 2023

Purpose:

To demonstrate the safety and efficacy of allogenic corneal inlays designed to increase the depth of focus (DoF) in treated eyes.

Settings:

Medipol University Hospital, Istanbul, Turkey.

Design:

Prospective case series.

Methods:

This study includes 50 eyes of 25 patients with a follow-up of 3 years. Emmetropic patients with presbyopia had implantation of allogenic corneal inlays in the nondominant eye. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and uncorrected near visual acuity (UNVA) were evaluated in all eyes. A subjective visual acuity test system (Multifocal Lens Analyzer 3.0 application) was used to analyze the DoF by measuring the defocus curves.

Results:

No significant difference between the treated and fellow eyes in UDVA and CDVA was found, whereas UNVA was significantly better in the treated eyes (P = .20, P = .07, P < .01, respectively). Comparing to the preoperative CDVA, there was a 1-line decrease in CDVA in 6 (%24) patients. The mean defocus curves reveal a DoF of 1.1 diopters (D) for the untreated eye at the logMAR = 0.2 threshold. By contrast, the mean DoF of the treated eye and binocularly was 2.8 D. The areas under the curve were significantly better in the near, intermediate, and total distances in the treated eyes, whereas it was better for the far distances in the untreated eyes. All values were significant (P = .023 total, P < .01 others).

Conclusions:

Allogenic presbyopic inlay implantation may be safe and provided a clinically and statistically significant increase in the DoF leading to good far, intermediate, and near-visual acuity in emmetropic presbyopic patients.
False-Positive 68Ga-DOTATATE Uptake in a Uterine Subserosal Fibroid Mimicking Mesenteric Neuroendocrine Tumor
Authors: Khalaj Kamand , Rowe Julie H. , Thupili Chakradhar R. , Tammisetti Varaha S.
Published: July 2023

68Ga-DOTATATE PET/CT is a highly sensitive and specific imaging modality in detecting neuroendocrine tumors. False-positive DOTATATE uptake poses diagnostic challenges. False-positive uptake in a uterine fibroid is the third most common location. We report the case of a 45-year-old woman with clinical concern for possible neuroendocrine tumor showing moderate focal DOTATATE uptake, which was initially thought of to be localized to mesentery on PET/CT images but was subsequently localized to a subserosal uterine fibroid following MRI. Patient underwent hysterectomy, further confirming that the uterine myometrial uptake is within the subserosal fibroid.
Lung Nodule as Culprit Lesion Causing Recurrent Tumor-Induced Osteomalacia Revealed by 68Ga-DOTATATE PET/CT
Authors: Zhang Yuwei , Wang Peipei , Jing Hongli
Published: July 2023

Neoplasms that cause tumor-induced osteomalacia are very rarely located in the lung. A 27-year-old man underwent a surgery in the right femoral head to remove the tumor that induced osteomalacia 8 years ago with complete symptomatic relief. However, his bone pain occurred again recently, which lead to suspicion of a recurrent tumor-induced osteomalacia. 68Ga-DOTATATE PET/CT images showed a pulmonary nodule with mildly increased uptake along with increased activity in the left foot. The pulmonary nodule was subsequently resected and was pathologically confirmed as a phosphaturic mesenchymal tumor. The symptoms were completely relieved postsurgery.
What We Know About Intracranial Hypertension in Children With Syndromic Craniosynostosis
Authors: Doerga Priya N. , Goederen Robbin de , van Veelen Marie-Lise C. , Joosten Koen F.M. , Tasker Robert C. , Mathijssen Irene M.J.
Published: July 2023

Objective:

A scoping review of literature about mechanisms leading to intracranial hypertension (ICH) in syndromic craniosynostosis (sCS) patients, followed by a narrative synopsis of whether cognitive and behavioral outcome in sCS is more related to genetic origins, rather than the result of ICH.

Methods:

The scoping review comprised of a search of keywords in EMBASE, MEDLINE, Web of science, Cochrane Central Register of Trials, and Google scholar databases. Abstracts were read and clinical articles were selected for full-text review and data were extracted using a structured template. A priori, the authors planned to analyze mechanistic questions about ICH in sCS by focusing on 2 key aspects, including (1) the criteria for determining ICH and (2) the role of component factors in the Monro-Kellie hypothesis/doctrine leading to ICH, that is, cerebral blood volume, cerebrospinal fluid (CSF), and the intracranial volume.

Results:

Of 1893 search results, 90 full-text articles met criteria for further analysis. (1) Invasive intracranial pressure measurements are the gold standard for determining ICH. Of noninvasive alternatives to determine ICH, ophthalmologic ones like fundoscopy and retinal thickness scans are the most researched. (2) The narrative review shows how the findings relate to ICH using the Monro-Kellie doctrine.

Conclusions:

Development of ICH is influenced by different aspects of sCS: deflection of skull growth, obstructive sleep apnea, venous hypertension, obstruction of CSF flow, and possibly reduced CSF absorption. Problems in cognition and behavior are more likely because of genetic origin. Cortical thinning and problems in visual function are likely the result of ICH.
Liver Histology Predicts Liver Regeneration and Outcome in ALPPS
Authors: Lopez-Lopez Victor , Linecker Michael , Caballero-Llanes Albert , Reese Tim , Oldhafer Karl J. , Hernandez-Alejandro Roberto , Tun-Abraham Mauro , Li Jun , Fard-Aghaie Mohammad , Petrowsky Henrik , Brusadin Roberto , Lopez-Conesa Asuncion , Ratti Francesca , Aldrighetti Luca , Ramouz Ali , Mehrabi Arianeb , Autran Machado Marcel , Ardiles Victoria , De Santibañes Eduardo , Marichez Arthur , Adam René , Truant Stéphanie , Pruvot Francois-René , Olthof Pim , Van Gulick Thomas , Montalti Roberto , Troisi Roberto I. , Kron Philipp , Lodge Peter , Kambakamba Patryk , Hoti Emir , Martinez-Caceres Carlos , de la Peña-Moral Jesus , Clavien Pierre-Alain , Robles-Campos Ricardo
Published: July 2023

Background and Aims:

Alterations in liver histology influence the liver´s capacity to regenerate, but the relevance of each of the different changes rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate.

Methods:

This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis.

Results:

In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs. 17 d, P˂0.01), low histological risk stage 2 (13 vs. 15 d, P˂0.01) and low pathological tumor risk (13 vs. 15 d, P˂0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight (r=−0.1 and r=−0.08, respectively), and future liver remnant (r=−0.15 and r=−0.06, respectively).

Conclusion:

ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage.
Early life impacts of maternal obesity: a window of opportunity to improve the health of two generations
Authors: Dearden Laura , Ozanne Susan E.
Published: July 2023

The number of pregnancies complicated by obesity is increasing in line with the worldwide obesity crisis; recent estimates suggest that in developed countries more than 50% of pregnancies are in women who are overweight or have obesity. Maternal obesity is associated with an increased risk of many adverse outcomes for both the mother and baby during pregnancy and birth. In addition to these immediate outcomes, maternal obesity before and during pregnancy is associated with an increased risk of offspring cardio-metabolic disease later in life. Studies comparing siblings discordant for
in utero
exposure to maternal obesity suggest this is not simply due to transmission of ‘obesogenic genes’ between mother and child or current lifestyle factors, but reflects a direct impact of the obese intrauterine environment on fetal development. This review will describe the long-term consequences of exposure to maternal obesity during development for the cardio-metabolic health of the offspring. It will also discuss the potential molecular mechanisms that underlie the increased risk of metabolic disease in offspring of mothers with obesity, and explore interventions that may be implemented during pregnancy to limit the impact of obesity on offspring long-term health.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Natural selection and human adiposity: crafty genotype, thrifty phenotype
Authors: Wells Jonathan C. K.
Published: July 2023

Evolutionary perspectives on obesity have aimed to understand how the genetic constitution of individuals has been shaped by selective pressures such as famine, predation or infectious disease. The dual intervention model assumes strong selection on lower and upper limits of adiposity, but negligible fitness implications for intermediate adiposity. These frameworks are agnostic to age, sex and condition. I argue that selection has favoured a ‘crafty genotype’—a genetic basis for accommodating variability in the ‘fitness value’ of fat through phenotypic plasticity, depending on the endogenous and exogenous characteristics of each individual. Hominin evolution occurred in volatile environments. I argue that the polygenetic basis of adiposity stabilizes phenotype in such environments, while also coordinating phenotypic variance across traits. This stability underpins reaction norms through which adiposity can respond sensitively to ecological factors. I consider how the fitness value of fat changes with age, sex and developmental experience. Fat is also differentially distributed between peripheral and abdominal depots, reflecting variable prioritization of survival versus reproduction. Where longevity has been compromised by undernutrition, abdominal fat may promote immediate survival and fitness, while long-term cardiometabolic risks may never materialize. This approach helps understand the sensitivity of adiposity to diverse environmental factors, and why the health impacts of obesity are variable.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Clinical and genomic diversity ofTreponema pallidum subsp. pallidum:A global, multi-center study of early syphilis to inform vaccine research
Authors: Seña Arlene C. , Matoga Mitch M. , Yang Ligang , Lopez-Medina Eduardo , Aghakanian Farhang , Chen Jane S. , Bettin Everton B. , Caimano Melissa J. , Chen Wentao , Garcia-Luna Jonny A. , Hennelly Christopher M. , Jiang Yinbo , Juliano Jonathan J. , Pospíšilová Petra , Ramirez Lady , Šmajs David , Tucker Joseph D. , Cely Fabio Vargas , Zheng Heping , Hoffman Irving F. , Yang Bin , Moody M. Anthony , Hawley Kelly L. , Salazar Juan C. , Radolf Justin D. , Parr Jonathan B.
Published: July 2023

Background

The continuing increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. We conducted a multi-center, observational study to exploreTreponema pallidumsubsp.pallidum(TPA) molecular epidemiology essential for vaccine research by analyzing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data.

Methods

We enrolled patients with primary (PS), secondary (SS) or early latent (ELS) syphilis from clinics in China, Colombia, Malawi and the United States between November 2019 - May 2022. Inclusion criteria included age ≥18 years, and syphilis confirmation by direct detection methods and/or serological testing.TPAdetection and WGS were conducted on lesion swabs, skin biopsies/scrapings, whole blood, and/or rabbit-passaged isolates. We compared our WGS data to publicly available genomes, and analysedTPApopulations to identify mutations associated with lineage and geography.

Findings

We screened 2,820 patients and enrolled 233 participants - 77 (33%) with PS, 154 (66%) with SS, and two (1%) with ELS. Median age of participants was 28; 66% werecis-gender male, of which 43% reported identifying as “gay”, “bisexual”, or “other sexuality”. Among all participants, 56 (24%) had HIV co-infection. WGS data from 113 participants demonstrated a predominance of SS14-lineage strains with geographic clustering. Phylogenomic analysis confirmed that Nichols-lineage strains are more genetically diverse than SS14-lineage strains and cluster into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident byTPAlineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models demonstrated population-specific substitutions, some in outer membrane proteins (OMPs) of interest.

Interpretation

Our study involving participants from four countries substantiates the global diversity ofTPAstrains. Additional analyses to exploreTPAOMP variability within strains will be vital for vaccine development and improved understanding of syphilis pathogenesis on a population level.

Funding

National Institutes of Health, Bill and Melinda Gates Foundation
Prebiotic Supplements Correct Oral Probiotic Deficiency for Lasting Allergy Relief
Authors: Han Cliff Shunsheng
Published: July 2023

Allergic rhinitis has increased in the last fifty years from affecting less than a percent to more than twenty-six percent of the population. Today, more than one hundred million people in the US suffer from these seasonal or yearlong allergies. The hygiene hypothesis was proposed 30 years ago as a potential explanation for this phenomenon, and we built on that with the specific oral hygiene hypothesis. Our longitudinal pilot study suggested that oral probiotic deficiency is the cause of allergic rhinitis. This clinical trial served to verify our theory and evaluate the effectiveness of AllerPops for allergy relief. Through it, we show that AllerPops prebiotic supplements are effective in providing sustained allergy relief (p = 0.002) and can modulate oral beneficial bacteria that produce short-chain fatty acids (SCFA), such asFusobacteria, Butyrivibrio, andPeptostreptococcus. The clinical improvements correlated with changes in the relative abundance of probiotics significantly:Fusobacteria(R = 0.32, p = 0.009),Butyrivibrio(R = 0.25, p = 0.044), andPeptostreptococcus(R = 0.34, p = 0.005). These results point to the root cause of allergic rhinitis: the lack of oral probiotics that produce SCFA to pacify the immune systems. Future study of AllerPops’ theory will help society redefine the best oral hygiene practice to protect oral probiotics so that we may prevent allergic and autoimmune diseases and dental/gum infections. The trial was retrospectively registered atclinicaltrials.com, with registration numberNCT05956691, on 21/07/2023.
APOEloss-of-function variants: Compatible with longevity and associated with resistance to Alzheimer’s Disease pathology
Authors: Chemparathy Augustine , Guen Yann Le , Chen Sunny , Lee Eun-Gyung , Leong Lesley , Gorzynski John , Xu Guangxue , Belloy Michael , Kasireddy Nandita , Tauber Andrés Peña , Williams Kennedy , Stewart Ilaria , Wingo Thomas , Lah James , Jayadev Suman , Hales Chad , Peskind Elaine , Child Daniel D , Keene C Dirk , Cong Le , Ashley Euan , Yu Chang-En , Greicius Michael D.
Published: July 2023

The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer’s Disease (AD). Knockdown of this allele may provide a therapeutic strategy for AD, but the effect ofAPOEloss-of-function (LoF) on AD pathogenesis is unknown. We searched forAPOELoF variants in a large cohort of older controls and patients with AD and identified six heterozygote carriers ofAPOELoF variants. Five carriers were controls (ages 71-90) and one was an AD case with an unremarkable age-at-onset between 75-79. TwoAPOEε3/ε4 controls (Subjects 1 and 2) carried a stop-gain affecting the ε4 allele. Subject 1 was cognitively normal at 90+ and had no neuritic plaques at autopsy. Subject 2 was cognitively healthy within the age range 75-79 and underwent lumbar puncture at between ages 75-79 with normal levels of amyloid. The results provide the strongest human genetics evidence yet available suggesting that ε4 drives AD risk through a gain of abnormal function and support knockdown ofAPOEε4 or its protein product as a viable therapeutic option.
Factors influencing COVID-19 vaccination decision-making among African American and Hispanic pregnant and postpartum women in Deep South
Authors: Zhang Ran , Byrd Tiffany , Qiao Shan , Torres Myriam E. , Li Xiaoming , Liu Jihong
Published: July 2023

Background

COVID-19 vaccination is vital for ending the pandemic but concerns about its safety among pregnant and postpartum women, especially among African American (AA) and Hispanic women, persist. This study aims to explore factors that influence vaccination decision-making among AA and Hispanic pregnant and postpartum women through women’s experiences and maternal care providers’ (MCPs) observations.

Methods

From January and August 2022, we conducted semi-structured interviews with AA and Hispanic women and MCPs. Participants were recruited from obstetric and pediatric clinics in South Carolina, and all births took place after March 2020. Thematic analysis was employed for data analysis.

Results

The study involved 19 AA and 20 Hispanic women, along with 9 MCPs, and revealed both barriers and facilitators to COVID-19 vaccination. The factors that influence pregnant and postpartum women’s decision about COVID-19 vaccine uptake included: 1) awareness of health threats associated with COVID-19 vaccines, 2) vaccine availability and accessibility, 3) vaccine-related knowledge and exposure to misinformation, 4) concerns regarding pre-existing health conditions and potential side effects of COVID-19 vaccines, 5) emotional factors associated with vaccination decision-making processes, 6) concerns about the well-being of infants, 7) cultural perspectives, and 8) encouragement by trusted supporters.

Conclusion

Findings suggest that reliable information, social support, and trusted doctors’ advice can motivate COVID-19 vaccination. However, barriers such as misinformation, mistrust in the health care system, and fears related to potential side effects impede vaccination uptake among AA and Hispanic pregnant and postpartum women. Future interventions should target these barriers, along with health disparities, involve trusted doctors in outreach, and initiate vaccine conversations to promote vaccination among this population.
Incubation-period estimates of Omicron (BA.1) variant from Taiwan, December 2021–January 2022, and its comparison to other SARS-CoV-2 variants: a statistical modeling, systematic search and meta-analysis
Authors: Akhmetzhanov Andrei R. , Cheng Hao-Yuan , Dushoff Jonathan
Published: July 2023

Background

The ongoing COVID-19 pandemic has seen several variants of concern, including the Omicron (BA.1) variant which emerged in October 2021. Accurately estimating the incubation period of these variants is crucial for predicting disease spread and formulating effective public health strategies. However, existing estimates often conflict because of biases arising from the dynamic nature of epidemic growth and selective inclusion of cases. This study aims to accurately estimate of the Omicron (BA.1) variant incubation period based on data from Taiwan, where disease incidence remained low and contact tracing was comprehensive during the first months of the Omicron outbreak.

Methods

We reviewed 100 contact-tracing records for cases of the Omicron BA.1 variant reported between December 2021 and January 2022, and found enough information to analyze 70 of these. The incubation period distribution was estimated by fitting data on exposure and symptom onset within a Bayesian mixture model using gamma, Weibull, and lognormal distributions as candidates. Additionally, a systematic literature search was conducted to accumulate data for estimates of the incubation period for Omicron (BA.1/2, BA.4/5) subvariants, which was then used for meta-analysis and comparison.

Results

The mean incubation period was estimated at 3.5 days (95% credible interval: 3.1–4.0 days), with no clear differences when stratified by vaccination status or age. This estimate aligns closely with the pooled mean of 3.4 days (3.0–3.8 days) obtained from a meta-analysis of other published studies on Omicron subvariants.

Conclusions

The relatively shorter incubation period of the Omicron variant, as compared to previous SARS-CoV2 variants, implies its potential for rapid spread but also opens the possibility for individuals to voluntarily adopt shorter, more resource-efficient quarantine periods. Continual updates to incubation period estimates, utilizing data from comprehensive contact tracing, are crucial for effectively guiding these voluntary actions and adjusting high socio-economic cost interventions.
Synergistic efficacy of tigecycline combined with apramycin againsttet(X)-harboringAcinetobacter spp.
Authors: Liu Juan , Zheng Si-Lin , Wu Jing-Jing , Zheng Mei , Cai Da-Tong , Zhang Yan , Sun Jian , Liu Ya-Hong , Liao Xiao-Ping , Yu Yang
Published: July 2023

The emergence of the wide variety of novel tigecycline resistancetet(X) variants includingtet(X3),tet(X4),tet(X5) andtet(X6) has posed a significant challenge to the clinical treatment of multidrug-resistant bacterial infections and represents a serious threat to global public health. The purpose of this study was to evaluate the synergism of tigecycline combined with other antibiotics as a means of overcomingtet(X)-mediated resistance inAcinetobacter spp. We found that the combinations of tigecycline with apramycin or amikacin exhibited synergistic activity againsttet(X)-harboringAcinetobacter spp. with FICI values of 0.088 and 0.625, respectively. The MICTGCdecreased >5-fold decrease in the presence of subinhibitory levels of apramycin. This combination was shown to be a therapeutically effective synergism using bothin vitroandin vivo(mouse thigh infection model) assays and delayed the increase of MIC values over time. This study highlights the synergism of tigecycline in combination with apramycin which offers a viable therapeutic alternative for infections caused bytet(X)-harboringAcinetobacter.
Slow conduction and spatial dispersion of repolarization are intrinsic properties of cardiomyocyte electrophysiology that contribute to proarrhythmia in an iPSC model of hypertrophic cardiomyopathy
Authors: Lim Seakcheng , Mangala Melissa M. , Holliday Mira , Szappanos Henrietta Cserne , Ross Samantha B. , Liang Whitney , Ranpura Ginell N. , Vandenberg Jamie I , Semsarian Christopher , Hill Adam P. , Hool Livia C.
Published: July 2023

Hypertrophic cardiomyopathy (HCM) is an inherited heart muscle disease; characterised by left ventricular wall thickening, cardiomyocyte disarray, and fibrosis, and is associated with arrhythmias, heart failure and sudden death. However, it is unclear to what extent the electrophysiological disturbances that lead to sudden death occur secondary to the structural changes in the myocardium, or as a result of intrinsic properties of the HCM cardiomyocyte. In this study, we used an induced pluripotent stem cell model of the Arg403Gln variant in myosin heavy chain 7 (MYH7) to study ‘tissue level’ electrophysiological properties of HCM cardiomyocytes. For the first time, we show significant slowing of conduction velocity and an increase in local spatial dispersion of repolarisation - both well-established substrates for arrhythmia - in monolayers of HCM cardiomyocytes. Analysis of rhythmonome protein expression in R403Q cardiomyocytes revealed dramatically reduced connexin-43, sodium channels, and inward rectifier channels – a three-way hit that combines to reduce electrotonic coupling between HCM cardiomyocytes and slow cardiac conduction. Our data therefore represent a novel, biophysical basis for arrhythmia in HCM, that is intrinsic to cardiomyocyte electrophysiology. Later in the progression of the disease, these proarrhythmic electrical phenotypes may be accentuated by fibrosis and myocyte disarray to contribute to sudden death in HCM patients.
Impact of Kaposi Sarcoma on Quality of Life Amongst HIV-infected Adults Initiating Antiretroviral Therapy in East Africa
Authors: Lu Scott , Laker-Oketta Miriam , Byakwaga Helen , Glidden David , Mwebesa Bwana , Muzoora Conrad , Maurer Toby , Assenzio Melissa , Hunt Peter , Bangsberg David , Haberer Jessica , Martin Jeffrey
Published: July 2023

BACKGROUND

In sub-Saharan Africa, increased antiretroviral therapy (ART) availability has improved survival after diagnosis of Kaposi sarcoma (KS) compared to the pre-ART era, but mortality among patients with KS is still considerably higher than HIV-infected persons without KS. Furthermore, among those patients with KS who are treated initially with ART without adjunct chemotherapy and who do survive, little is known about how well they function and feel — quality of life (QOL) — compared to those without KS.

METHODS

Among HIV-infected adults initiating ART in two prospective studies in Uganda, we compared those presenting with KS to those without KS. QOL was measured using the Medical Outcomes Survey-HIV instrument prior to ART initiation and at 16, 32, and 48 weeks thereafter; higher scores indicate better QOL. To ascertain the independent effect of KS versus non-KS on 11 domains of QOL and two summary scores, we created mixed effects models adjusted for directed acyclic graph-informed confounders.

RESULTS

We examined 224 participants with KS and 730 without KS, among whom 64% were women and median age was 34 years. Prior to ART initiation, participants had a median CD4+ T count of 159 cells/mm3and plasma HIV RNA of 5.1 log10copies/ml. In adjusted analyses prior to ART initiation, those with KS had lower mean scores in 8 of 11 QOL domains and both physical and mental health summary scores compared to those without KS. After 48 weeks of ART, those with KS had higher mean QOL scores compared those without KS in 4 domains and the mental health summary score, and lower scores in only one domain. There was no significant difference in 6 domains and the physical health summary score,

CONCLUSIONS

Amongst HIV-infected adults in East Africa, at time of ART initiation, those with KS had worse mean QOL compared to those without KS. Over the first year of ART, those with KS became comparable to or exceeded those without KS in most QOL domains. The findings indicate that some patients with KS can be treated with ART alone and further emphasize the need to predict those who will do well with ART alone versus those who need additional initial therapy.
Mental health status and related factors influencing healthcare workers during the COVID-19 pandemic: a systematic review and meta-analysis
Authors: Huang Jia , Huang Zhu-Tang , Sun Xin-Ce , Chen Ting-Ting , Wu Xiao-Tian
Published: July 2023

Background

The mental health of healthcare workers during the coronavirus-2019 pandemic was seriously affected, and the risk of mental health problems was high. The present study sought to systematically evaluate the mental health problems of healthcare workers worldwide during the pandemic and to determine the latest global frequency of COVID-19 associated mental health problems.

Methods

Data in the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Elsevier, MEDLINE, PubMed, PsycINFO and the Web of Science before November 11, 2022, were systematically searched. Cohort, case-control and cross-sectional studies were included. The meta-analysis used a random effects model to synthesize the comprehensive prevalence rate of mental health problems. Subgroup analyses were performed based on time of data collection; whether the country was or was not developed; continent; doctors and nurses; doctors/nurses vs. other healthcare workers; and psychological evaluation scale.

Results

A total of 161 studies were included, including 341,014 healthcare workers worldwide, with women accounting for 82.8%. Occupationally, 16.2% of the healthcare workers were doctors, 63.6% were nurses and 13.3% were other medical staff. During the pandemic, 47% (95% confidence interval [CI], 35-60%) of healthcare workers reported job burnout, 38% (95% CI, 35-41%) experienced anxiety, 34% (95% CI 30-38%) reported depression, 30% (95% CI, 29-31%) had acute stress disorder, and 26% (95% CI, 21-31%) had post-traumatic stress disorder.

Conclusions

The study found that there were common mental health problems among health care workers during the COVID-19 pandemic. The most common was job burnout, followed by anxiety, depression, acute stress and post-traumatic stress disorder. Although the global pandemic has been brought under control, its long-term impact on the mental health of healthcare workers cannot be ignored. Additional research is required to develop measures to prevent, monitor and treat psychological disorders among healthcare workers.