bluuebunny/crossref_metadata_2025 huggingface dataset:
Overlapping authorities, vikings in Frisia and the church of Utrecht
Authors: McNair Fraser
Published: July 2024

In 858 King Lothar II granted Bishop Hunger of Utrecht the abbey of Sint Odiliënberg to serve as a refuge against viking attacks. This article examines the political circumstance surrounding this event, arguing that the Utrecht clergy’s relocation was not a straightforward response to viking violence but was instead the result of pressures upon them caused by Frisia’s place at the centre of difference circles of overlapping authority. Through taking Frisia’s role in multiple polities and sub-polities seriously, I offer a new interpretation of the events of 858 and point to some further implications for earlier medieval politics.
A secularizing society? Case studies of English northern industrial towns in the 1950s
Authors: Field Clive
Published: July 2024

The religious historiography of Britain during the 1950s remains underdeveloped. Such scholarship as there is has drawn disproportionately upon national church statistics and opinion polls. In this article, the findings of three contemporaneous studies of religion in northern industrial towns are presented: Rawmarsh and Scunthorpe (1954–6), Billingham (1957–9), and Bolton (1960). Sundry indicators are illuminated, including churchgoing and rites of passage. No support is found for the claim that the 1950s were a decade of ‘religious revival’. Mainstream Protestantism was at an increasingly low ebb, and Catholicism was soon to feel the chill winds of secularization also.
Sorbitol mediates age-dependent changes in apple plant growth strategy through gibberellin signaling
Authors: Jia Xumei , Xu Shuo , Wang Fei , Jia Yiwei , Qing Yubin , Gao Tengteng , Zhang Zhijun , Liu Xiaomin , Yang Chao , Ma Fengwang , Li Chao
Published: July 2024

Plants experience various age-dependent changes during juvenile to adult vegetative phase. However, the regulatory mechanisms orchestrating the changes remain largely unknown in apple (Malus domestica). This study showed that tissue-cultured apple plants at juvenile, transition, and adult phase exhibit age-dependent changes in their plant growth, photosynthetic performance, hormone levels, and carbon distribution. Moreover, this study identified an age-dependent gene, sorbitol dehydrogenase (MdSDH1), a key enzyme for sorbitol catabolism, highly expressed in the juvenile phase in apple. Silencing MdSDH1 in apple significantly decreased the plant growth and GA3 levels. However, exogenous GA3 rescued the reduced plant growth phenotype of TRV-MdSDH1. Biochemical analysis revealed that MdSPL1 interacts with MdWRKY24 and synergistically enhance the repression of MdSPL1 and MdWRKY24 on MdSDH1, thereby promoting sorbitol accumulation during vegetative phase change. Exogenous sorbitol application indicated that sorbitol promotes the transcription of MdSPL1 and MdWRKY24. Notably, MdSPL1-MdWRKY24 module functions as key repressor to regulate GA-responsive gene, Gibberellic Acid-Stimulated Arabidopsis (MdGASA1) expression, thereby leading to a shift from the quick to the slow-growth strategy. These results reveal the pivotal role of sorbitol in controlling apple plant growth, thereby improving our understanding of vegetative phase change in apple.
Establishment of a Hepatitis B Virus Reporter System Harboring an HiBiT-Tag in the PreS2 Region
Authors: Nakaya Yuki , Onomura Daichi , Hoshi Yuji , Yamagata Tomoko , Morita Hiromi , Okamoto Hiroaki , Murata Kazumoto
Published: July 2024

Background

Approximately 296 million people have chronic hepatitis B (CHB) caused by hepatitis B virus (HBV). Current standard treatment, nucleos(t)ide analogs, are not efficient enough to eradicate HBV from the hepatocytes. Thus, developing new drugs for CHB is needed to achieve complete cure.

Methods

Here we established a novel HBV reporter system, HBV-HiBiT-PS2, to screen new drugs for CHB. HBV-HiBiT-PS2 was constructed by adding an HiBiT-tag at the 5′ end of preS2 and introduced this into HepG2-NTCP cells. Culture supernatant containing HBV-HiBiT-PS2 virions was fractionated by sucrose density gradient ultracentrifugation to characterize their components. Replication kinetics and reporter function of HBV-HiBiT-PS2 were determined by analyzing the parameters for HBV replication in the presence or absence of HBV inhibitors.

Results

HBV-HiBiT-PS2 could be used for monitoring most of the replication cycle of HBV. The effects of well-characterized HBV inhibitors could be evaluated by the HiBiT activity. HBV-HiBiT-PS2 could be specialized for screening secretion inhibitors for hepatitis B surface antigen (HBsAg) because most of the HiBiT activity was derived from subviral particles which are the multimers of HBsAg.

Conclusions

We demonstrated that HBV-HiBiT-PS2 would be a robust tool for screening novel drugs, especially HBsAg secretion inhibitors, targeted against CHB.
A comprehensive, large-scale analysis of “terroir” cheese and milk microbiota reveals profiles strongly shaped by both geographical and human factors
Authors: Irlinger Françoise , Mariadassou Mahendra , Dugat-Bony Eric , Rué Olivier , Neuvéglise Cécile , Renault Pierre , Rifa Etienne , Theil Sébastien , Loux Valentin , Cruaud Corinne , Gavory Frederick , Barbe Valérie , Lasbleiz Ronan , Gaucheron Frédéric , Spelle Céline , Delbès Céline
Published: July 2024

An exhaustive analysis was performed on more than 2000 microbiotas from French Protected Designation of Origin (PDO) cheeses, covering most cheese families produced throughout the world. Thanks to a complete and accurate set of associated metadata, we have carried out a deep analysis of the ecological drivers of microbial communities in milk and “terroir” cheeses. We show that bacterial and fungal microbiota from milk differed significantly across dairy species while sharing a core microbiome consisting of four microbial species. By contrast, no microbial species were detected in all ripened cheese samples. Our network analysis suggested that the cheese microbiota was organized into independent network modules. These network modules comprised mainly species with an overall relative abundance lower than 1%, showing that the most abundant species were not those with the most interactions. Species assemblages differed depending on human drivers, dairy species, and geographical area, thus demonstrating the contribution of regional know-how to shaping the cheese microbiota. Finally, an extensive analysis at the milk-to-cheese batch level showed that a high proportion of cheese taxa were derived from milk under the influence of the dairy species and protected designation of origin.
Is percutaneous nephrolithotripsy feasible in ipsilateral lumbar incisional hernia? A report of two patients
Authors: Do Anh Toan , Nguyen Huynh Dang Khoa , Nguyen Ngoc Thai
Published: July 2024

Incisional hernia refers to an abdominal wall defect at the site of a previous surgical incision. In this paper, we describe two patients who previously underwent open kidney stone surgery several years ago and had the ipsilateral recurrent stones. They were both managed by a mini percutaneous nephrolithotripsy (PCNL) to treat kidney stones. Case 1 was a 50-year-old female with right recurrent staghorn stones after 5 years of open surgery and required two PCNL procedures to achieve stone-free status. Case 2 was a 74-year-old male with significant comorbidities who had a right 27 mm recurrent kidney stone after 10 years of open nephrolithotomy. Both patients experienced no postoperative complications after PCNL. These cases show that in cases of lumbar incisional scar hernias, mini PCNL with ultrasound guidance and proper patient positioning can be an optimal approach for kidney stone treatment.
‘The Stamp of Their Own Iniquity’: Ottobah Cugoano on the Mark of Cain, Noah’s Curse, and Enslavers
Authors: Schipper Jeremy
Published: July 2024

Recently, Nyasha Junior has argued that interpretations of Cain by Black interpreters should not be understood as merely a reaction or corrective to anti-Black aetiological theories about the mark of Cain (Gen. 4:15). Surveying a range of 19th- and early 20th-century Black interpreters, Junior showed how they used the story of Cain to account for the violence that they believed is inherent in white people. In this article, I provide further evidence for this reading of Cain’s violence as an aetiological explanation for white violence. I analyse Ottobah Cugoano’s discussion of Cain in his Thoughts and Sentiments on the Evil and Wicked Traffic of the Slavery: and Commerce of the Human Species (1787) as a further example of this type of interpretation within African diasporic writings. In unmooring the mark from racial origins and linking it closely to racial violence, in part through a connection that Cugoano makes with Noah’s curse of his grandson Canaan in Genesis 9, elements of Cugoano’s argument anticipate the 19th- and early 20th-century Black interpreters who, as Junior discussed, argue that white people resemble Cain in their inherently violent tendencies.
Dietary iron intake has long-term effects on the fecal metabolome and microbiome
Authors: Kostenko Anastasiia , Zuffa Simone , Zhi Hui , Mildau Kevin , Raffatellu Manuela , Dorrestein Pieter C , Aron Allegra T
Published: July 2024

Iron is essential for life, but its imbalances can lead to severe health implications. Iron deficiency is the most common nutrient disorder worldwide, and iron dysregulation in early life has been found to cause long-lasting behavioral, cognitive, and neural effects. However, little is known about the effects of dietary iron on gut microbiome function and metabolism. In this study, we sought to investigate the impact of dietary iron on the fecal metabolome and microbiome by using mice fed with three diets with different iron content: an iron deficient, an iron sufficient (standard), and an iron overload diet for 7 weeks. Additionally, we sought to understand whether any observed changes would persist past the 7-week period of diet intervention. To assess this, all feeding groups were switched to a standard diet, and this feeding continued for an additional 7 weeks. Analysis of the fecal metabolome revealed that iron overload and deficiency significantly alter levels of peptides, nucleic acids, and lipids, including di- and tri-peptides containing branched-chain amino acids, inosine and guanosine, and several microbial conjugated bile acids. The observed changes in the fecal metabolome persist long after the switch back to a standard diet, with the cecal gut microbiota composition and function of each group distinct after the 7-week standard diet wash-out. Our results highlight the enduring metabolic consequences of nutritional imbalances, mediated by both the host and gut microbiome, which persist after returning to the original standard diets.
Weak-cooperative binding of a long single-stranded DNA chain on a surface
Authors: Nava Giovanni , Carzaniga Thomas , Casiraghi Luca , Bot Erik , Zanchetta Giuliano , Damin Francesco , Chiari Marcella , Weber Gerald , Bellini Tommaso , Mollica Luca , Buscaglia Marco
Published: July 2024

Binding gene-wide single-stranded nucleic acids to surface-immobilized complementary probes is an important but challenging process for biophysical studies and diagnostic applications. The challenge comes from the conformational dynamics of the long chain that affects its accessibility and weakens its hybridization to the probes. We investigated the binding of bacteriophage genome M13mp18 on several different 20-mer probes immobilized on the surface of a multi-spot, label-free biosensor, and observed that only a few of them display strong binding capability with dissociation constant as low as 10 pM. Comparing experimental data and computational analysis of the M13mp18 chain structural features, we found that the capturing performance of a specific probe is directly related to the multiplicity of binding sites on the genomic strand, and poorly connected with the predicted secondary and tertiary structure. We show that a model of weak cooperativity of transient bonds is compatible with the measured binding kinetics and accounts for the enhancement of probe capturing observed when more than 20 partial pairings with binding free energy lower than -10 kcal mol−1 are present. This mechanism provides a specific pattern of response of a genomic strand on a panel of properly selected oligomer probe sequences.
Kidney outcomes with SGLT2 inhibitor versus DPP4 inhibitor use in older adults with diabetes
Authors: Suzuki Yuta , Kaneko Hidehiro , Okada Akira , Komuro Jin , Ko Toshiyuki , Fujiu Katsuhito , Takeda Norifumi , Morita Hiroyuki , Nishiyama Akira , Ieda Masaki , Node Koichi , Yasunaga Hideo , Nangaku Masaomi , Komuro Issei
Published: July 2024

Background

While the kidney-protective effects of sodium–glucose co-transporter 2 (SGLT2) inhibitors have attracted much attention, there are limited real-world clinical data examining the effects of SGLT2 inhibitors on kidney function in older individuals. We aimed to compare the kidney outcomes between SGLT2 inhibitor and dipeptidyl peptidase 4 (DPP4) inhibitor use in older adults with diabetes.

Methods

Using a nationwide claims database, we studied 6354 older adults (≥60 years of age) who had diabetes and were newly initiated on SGLT2 inhibitors or DPP4 inhibitors. A 1:4 propensity score matching algorithm was used to compare changes in estimated glomerular filtration rate (eGFR) between SGLT2 inhibitor and DPP4 inhibitor users. The primary outcome was a decrease in the rate of eGFR, which was obtained using a linear mixed-effects model with an unstructured covariance.

Results

Following propensity score matching, 6354 individuals including 1271 SGLT2 inhibitor users and 5083 DPP4 inhibitor users {median age 68 years [interquartile range (IQR) 65–70], male 60.4%, median eGFR 69.0 ml/min/1.73 m2 [IQR 59.1–79.0], median haemoglobin A1c [HbA1c] 6.9% [IQR 6.5–7.4]} were analysed. SGLT2 inhibitor users had a slower eGFR decline than did DPP4 inhibitor users [−0.97 ml/min/1.73 m2/year (95% CI −1.24 to −0.70) versus −1.83 ml/min/1.73 m2/year (95% CI −1.97 to −1.69); P for interaction <.001]. This finding remained consistent across subgroups based on age, sex, body mass index, HbA1c level, renin–angiotensin system inhibitor use and baseline eGFR. Additionally, the risk of a ≥20%, ≥30% and ≥40% decrease in eGFR from baseline was significantly lower in SGLT2 inhibitor users than in DPP4 inhibitor users.

Conclusions

Our analysis, utilizing a nationwide epidemiological dataset, demonstrated that the decrease in eGFR was slower in individuals ≥60 years of age with diabetes who were prescribed SGLT2 inhibitors compared with those prescribed DPP4 inhibitors, suggesting a potential advantage of SGLT2 inhibitors for kidney outcomes even in older individuals with diabetes.
Rising to the Challenge: An ID Provider–Led Initiative to Address Penicillin Allergy Labels at a Large Veterans Affairs Medical Center
Authors: Arasaratnam Reuben J , Guastadisegni Jessica M , Kouma Marcus A , Maxwell Daniel , Yang Linda , Storey Donald F
Published: July 2024

Background

Given the negative consequences associated with a penicillin allergy label, broader penicillin allergy delabeling initiatives are highly desirable but hindered by the shortage of allergists in the United States. To address this problem at our facility, the infectious diseases section introduced a quality improvement initiative to evaluate and remove allergy labels among inpatient veterans.

Methods

Between 15 November 2022 and 15 December 2023, we identified inpatients with a penicillin allergy label. We subsequently interviewed eligible candidates to stratify penicillin allergy risk and attempt to remove the allergy label directly via chart review, following inpatient oral amoxicillin challenge or outpatient community care allergy referral. Delabeling outcomes, subsequent penicillin-class prescriptions, and relabeling were tracked after successful allergy label removal.

Results

We screened 272 veterans, of whom 154 were interviewed for this intervention. A total of 53 patients were delabeled: 26 directly, 23 following oral amoxicillin challenge, and 4 following outpatient allergy referrals. Of the patients who were delabeled, 25 received subsequent penicillin-class prescriptions. No adverse reactions occurred following inpatient oral amoxicillin challenges. Patients with a low-risk penicillin allergy history were more likely to undergo a challenge if admitted with an infectious diseases–related condition. Only 1 inappropriate relabeling event occurred during the study period, which was subsequently corrected.

Conclusions

An infectious diseases provider–led initiative resulted in penicillin allergy label removal in more than one third of inpatients evaluated using direct removal or oral amoxicillin challenge. Efforts focused on patients who had been admitted for infections were particularly successful.
Beyond the Standard GWAS—A Guide for Plant Biologists
Authors: Clauw Pieter , Ellis Thomas James , Liu Hai-Jun , Sasaki Eriko
Published: July 2024

Classic genome-wide association studies (GWAS) look for associations between individual single-nucleotide polymorphisms (SNPs) and phenotypes of interest. With the rapid progress of high-throughput genotyping and phenotyping technologies, GWAS have become increasingly powerful for detecting genetic determinants and their molecular mechanisms underpinning natural phenotypic variation. However, GWAS frequently yield results with neither expected nor promising loci, nor any significant associations. This is often because associations between SNPs and a single phenotype are confounded, for example with the environment, other traits or complex genetic structures. Such confounding can mask true genotype–phenotype associations, or inflate spurious associations. To address these problems, numerous methods have been developed that go beyond the standard model. Such advanced GWAS models are flexible and can offer improved statistical power for understanding the genetics underlying complex traits. Despite this advantage, these models have not been widely adopted and implemented compared to the standard GWAS approach, partly because this literature is diverse and often technical. In this review, our aim is to provide an overview of the application and the benefits of various advanced GWAS models for handling complex traits and genetic structures, targeting plant biologists who wish to carry out GWAS more effectively.
Trade Wars, Nominal Rigidities, and Monetary Policy
Authors: Auray Stéphane , Devereux Michael B , Eyquem Aurélien
Published: July 2024

This paper shows that the outcome of trade wars for tariffs and welfare will be affected by the monetary policy regime. The key message is that trade policy interacts with monetary policy in a way that magnifies the welfare costs of discretionary monetary policy in an international setting. If countries follow monetary policies of flexible inflation targeting, trade wars are relatively mild, with low equilibrium tariffs and small welfare costs. Discretionary monetary policies imply much higher tariffs, high inflation rates, and substantially larger welfare costs. We quantify the effects of a global trade war among major economies using estimates of trade elasticities, economic size, net foreign assets, and trade openness. We find large welfare benefits of an inflation targeting monetary policy for all countries.
Introduction to the Special Issue: The Lives (and Futures) of Black Children and Youth
Authors: Brooms Derrick R , Medford Marcelle M
Published: July 2024

As social science scholarship on Black children and youth continues to expand and explore their experiences, there still remains a need to investigate how families, communities, relationships, and social institutions impact their experiences. The theme for this special issue is inspired in part by our considerations of Black children’s and youth’s present realities and their futures. The editors of this volume are interested in creating space to analyze and theorize the radical possibilities for Black children to flourish in a world that typically ignores, marginalizes, and dismisses their plights and their promise. Privileging the agency of Black youth, the articles in this special issue provide nuanced accounts of how they make sense of many aspects of their lives and futures.
Exosomes derived from umbilical cord‐derived mesenchymal stem cells exposed to diabetic microenvironment enhance M2 macrophage polarization and protect against diabetic nephropathy
Authors: Su Wanlu , Yin Yaqi , Zhao Jian , Hu Ruofan , Zhang Haixia , Hu Jia , Ren Rui , Zhang Yue , Wang Anning , Lyu Zhaohui , Mu Yiming , Cheng Yu
Published: July 2024

The role of mesenchymal‐stem‐cell‐derived exosomes (MSCs‐Exo) in the regulation of macrophage polarization has been recognized in several diseases. There is emerging evidence that MSCs‐Exo partially prevent the progression of diabetic nephropathy (DN). This study aimed to investigate whether exosomes secreted by MSCs pre‐treated with a diabetic environment (Exo‐pre) have a more pronounced protective effect against DN by regulating the balance of macrophages. Exo‐pre and Exo‐Con were isolated from the culture medium of UC‐MSCs pre‐treated with a diabetic mimic environment and natural UC‐MSCs, respectively. Exo‐pre and Exo‐Con were injected into the tail veins of db/db mice three times a week for 6 weeks. Serum creatinine and serum urea nitrogen levels, the urinary protein/creatinine ratio, and histological staining were used to determine renal function and morphology. Macrophage phenotypes were analyzed by immunofluorescence, western blotting, and quantitative reverse transcription polymerase chain reaction. In vitro, lipopolysaccharide‐induced M1 macrophages were incubated separately with Exo‐Con and Exo‐pre. We performed microRNA (miRNA) sequencing to identify candidate miRNAs and predict their target genes. An miRNA inhibitor was used to confirm the role of miRNAs in macrophage modulation. Exo‐pre were more potent than Exo‐Con at alleviating DN. Exo‐pre administration significantly reduced the number of M1 macrophages and increased the number of M2 macrophages in the kidney compared to Exo‐Con administration. Parallel outcomes were observed in the co‐culture experiments. Moreover, miR‐486‐5p was distinctly expressed in Exo‐Con and Exo‐pre groups, and it played an important role in macrophage polarization by targeting PIK3R1 through the PI3K/Akt pathway. Reducing miR‐486‐5p levels in Exo‐pre abolished macrophage polarization modulation. Exo‐pre administration exhibited a superior effect on DN by remodeling the macrophage balance by shuttling miR‐486‐5p, which targets PIK3R1.
Update on antineutrophil cytoplasmic autoantibody vasculitis in children
Authors: Bloom Jessica L. , Wu Eveline Y.
Published: July 2024

Purpose of review

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is often organ- or life-threatening in children and impacts them during important periods of psychosocial and physical development. This review covers recent advances in the pathophysiology, diagnosis, management, and outcomes of AAV in children and highlights the ongoing need for funding and increased research collaboration.

Recent findings

Recent work has improved our understanding of AAV disease pathogenesis, potentially identifying new biomarkers and therapeutic targets. Collaborative clinical studies have also highlighted the variable manifestations in children and identified potential factors associated with poorer outcomes. Consensus-based treatment guidelines are also appearing, but clinical trials are still essential to better understanding treatment efficacy and safety in children affected by AAV. New, validated outcome measures, including those that are patient-reported, will facilitate these much-needed clinical trials in pediatric AAV.

There is a continued need for more rigorous study in pediatric AAV, however, there is certainly excitement with the increase in recent research relevant to the pediatric population.
Undiagnosed Behçet’s disease presenting as Fournier’s gangrene in undiagnosed Behçet’s disease: a case report of a young adult male
Authors: Hodaifa Yara , Tarcha Raghad , Alghawe Fatima , Btrush Sana , Batha Wafaa , Kudsi Maysoun
Published: July 2024

Introduction and importance:

Behçet’s disease is a rare systemic condition, with the mean age of patients being ~30 years. It affects men more than women. Behçet’s disease should be considered in any patient with a systemic inflammatory disease characterized by recurrent orogenital ulcers and uveitis. Fournier’s gangrene is a rare life-threatening bacterial genital infection that acquires at any age with male predominance.

Case presentation:

A healthy 32-year-old male presented with fatigue, fever, oral ulcers, and discrete scrotal ulcers. He had Fournier’s gangrene and a new diagnosis of Behçet’s disease. He was treated with intravenous antibiotics with surgical debridement. Before discharge, the patient was commenced on 1 mg/day of colchicine. During the follow-up visits, we noted small ulcerations without necrosis on the scrotum, which we started with oral prednisolone and oral methotrexate. He remains under their care 6 months later.

Clinical discussion:

The patient had recurrent oral ulcerations followed by genital aphthous ulceration and acneiform eruptions that met Behçet’s diagnosing criteria. Fournier’s gangrene on the scrotum was diagnosed due to the physical examination, radiological findings, and histological findings. A PubMed search reveals one similar case report. This patient’s only risk factor for Bechet’s was his ethnicity and male gender for Fournier’s gangrene.

Conclusion:

The young adult patient presented unusually, with a diagnosis of Fournier’s gangrene superimposed on undiagnosed Behçet’s disease. An understanding of the epidemiology and risk factors can help in the diagnosis of these rare pathologies.
Evaluating Child Passenger Restraint Use Education
Authors: Marsala Jeanne , Hightower Todd , Stucke Sheri , Trujillo Brittany , Malone Cheryl , Bertolani Jennifer , Jacobs Justin , Silverberg David , Rivera Nancy , Fiore Nicholas
Published: July 2024

BACKGROUND:

Despite recommendations and laws for child restraint use in motor vehicles, evidence of low restraint use remains, and there is a lack of evidence addressing the effectiveness of restraint use education.

OBJECTIVE:

This project aims to measure the impact of an education initiative on child passenger restraint use.

METHODS:

This pre- and postintervention study was conducted in six elementary schools in a Southwestern U.S. metropolitan area over 5 months from October 2022 to March 2023. Motor vehicle restraint use was collected from occupants arriving at elementary schools during the morning drop-off times. Participants were provided one-on-one education regarding child passenger safety guidelines and state laws. Comparison data were collected 1–3 weeks later at the same schools to evaluate the education provided.

RESULTS:

A total of 1,671 occupants in 612 vehicles were observed across six schools, with 343 adults and 553 children preintervention and 306 adults and 469 children postintervention. Overall restraint adherence in children improved postintervention from 42.3% to 56.1%, a 32.6% increase (p = < .001). In the primary age group of 4–8 years, restraint adherence improved postintervention from 34.8% to 54.2%, a 55.8% increase (p = <.001).

CONCLUSIONS:

The study results demonstrate that one-on-one education increases child passenger restraint use.
Outcome of patients with complete cleft lip and alveolus: 20-year follow-up
Authors: Hattori Yoshitsugu , Pai Betty Chien-Jung , Saito Takafumi , Chou Pang-Yun , Lu Ting-Chen , Chang Chun-Shin , Chen Yu-Ray , Lo Lun-Jou
Published: July 2024

Background:

Patients with cleft have functional and aesthetic impairment, and typically require several interventions as they grow. Long-term evaluation following a treatment protocol is essential, but such reports on patients with complete cleft lip and alveolus (CLA) are sparse in the literature.

Methods:

A retrospective review was conducted to all patients with complete CLA born between January 1995 and August 2002 and treated at our center. Patients who received continuous multidisciplinary team care until 20 years of age were included, and patients with cleft palate and syndromic abnormalities were excluded. Facial bone growth was evaluated using cephalometric analysis.

Results:

Eighty-seven and 11 patients with unilateral and bilateral CLA (UCLA and BCLA) were included respectively. All patients received one-stage cheiloplasty with primary rhinoplasty. Revisional lip/nose surgery was performed in 21.8 and 27.3% during growing age, and in 51.7 and 72.7% after skeletal maturity. Orthognathic surgery was performed in 20.7 and 27.3%. Compared with UCLA patients, BCLA had larger number of operations (3.0 versus 3.7, p = 0.03) and higher chance of receiving alveolar bone grafting twice (1.1% versus 36.4%, p < 0.01). Patients with complete CLA had less hypoplastic maxilla, and received smaller number of operations than complete cleft lip and palate.

Conclusion:

Complete CLA is a less severe form of cleft, but the patients still require multiple interventions. This review revealed certain suboptimal results, and modifications have been made in the treatment protocol. Longitudinal follow-up and periodic assessment help to establish an ideal therapeutic strategy and improve overall cleft care.
Dynamic Changes of the Genital Hiatus at the Time of Prolapse Surgery: 1-Year Follow-Up Study
Authors: Chang Olivia H. , Ferrando Cecile A. , Paraiso Marie Fidela R. , Propst Katie
Published: July 2024

Importance

The genital hiatus (GH) has been identified as a predictor of pelvic organ prolapse. An enlarged preoperative GH is a risk factor for recurrent prolapse after surgery.

Objective

The objective of this study was to determine the changes in preoperative and postoperative GH size compared with the intraoperative resting GH at 6 weeks and 12 months after native-tissue pelvic organ prolapse surgery.

Study Design

This was a descriptive analysis of a prospective cohort study of women undergoing native-tissue prolapse repair with apical suspension. Resting GH was obtained at the start and conclusion of surgery. Measurements were obtained preoperatively, and 6 weeks and 12 months postoperatively under Valsalva maneuver. Comparisons were made using pairedttests for the following time points: (1) preoperative measurements under Valsalva maneuver to resting presurgery measurements under anesthesia, and (2) resting postsurgery measurements under anesthesia to 6 weeks and 12 months postoperatively under Valsalva maneuver.

Results

Sixty-seven patients were included, with a median age of 66 years and median body mass index (calculated as weight in kilograms divided by height in meters squared) of 29.1. There was no significant difference in GH when measured preoperatively to resting presurgical measurements under anesthesia (P= 0.60). For all, the median GH was 3.0 cm at the conclusion of surgery and remained at 3.0 cm at 6 weeks and 12 months postoperatively. In patients who had a concurrent posterior colporrhaphy, the median resting postsurgery GH was 3.0 cm, then decreased to 2.5 cm at 6 weeks then 3.5 cm at 12 months under Valsalva.

Conclusions

Preoperative GH size under Valsalva maneuver and resting under anesthesia were comparable. For all patients undergoing native-tissue pelvic organ prolapse repair, the genital hiatus size remains the same from the intraoperative final resting measurements to the 6-week and 12-month measurements under Valsalva maneuver.
Recent insights in striated muscle laminopathies
Authors: Leconte Marine , Bonne Gisèle , Bertrand Anne T.
Published: July 2024

Purpose of review

To highlight recent insights in different aspects of striated muscle laminopathies (SMLs) related to LMNA mutations.

Recent findings

Clinical and genetic studies allow better patient management and diagnosis, with confirmation of ventricular tachyarrhythmias (VTA) risk prediction score to help with ICD implantation and development of models to help with classification of LMNA variants of uncertain significance. From a pathophysiology perspective, characterization of lamin interactomes in different contexts revealed new lamin A/C partners. Expression or function modulation of these partners evidenced them as potential therapeutic targets. After a positive phase 2, the first phase 3 clinical trial, testing a p38 inhibitor targeting the life-threatening cardiac disease of SML, has been recently stopped, thus highlighting the need for new therapeutic approaches together with new animal and cell models.

Since the first LMNA mutation report in 1999, lamin A/C structure and functions have been actively explored to understand the SML pathophysiology. The latest discoveries of partners and altered pathways, highlight the importance of lamin A/C at the nuclear periphery and in the nucleoplasm. Modulation of altered pathways allowed some benefits, especially for cardiac involvement. However, additional studies are still needed to fully assess treatment efficacy and safety.
Biomolecular condensates can function as inherent catalysts
Authors: Guo Xiao , Farag Mina , Qian Naixin , Yu Xia , Ni Anton , Ma Yuefeng , Yu Wen , King Matthew R. , Liu Vicky , Lee Joonho , Zare Richard N. , Min Wei , Pappu Rohit V. , Dai Yifan
Published: July 2024

We report the discovery that chemical reactions such as ATP hydrolysis can be catalyzed by condensates formed by intrinsically disordered proteins (IDPs), which themselves lack any intrinsic ability to function as enzymes. This inherent catalytic feature of condensates derives from the electrochemical environments and the electric fields at interfaces that are direct consequences of phase separation. The condensates we studied were capable of catalyzing diverse hydrolysis reactions, including hydrolysis and radical-dependent breakdown of ATP whereby ATP fully decomposes to adenine and multiple carbohydrates. This distinguishes condensates from naturally occurring ATPases, which can only catalyze the dephosphorylation of ATP. Interphase and interfacial properties of condensates can be tuned via sequence design, thus enabling control over catalysis through sequence-dependent electrochemical features of condensates. Incorporation of hydrolase-like synthetic condensates into live cells enables activation of transcriptional circuits that depend on products of hydrolysis reactions. Inherent catalytic functions of condensates, which are emergent consequences of phase separation, are likely to affect metabolic regulation in cells.
Vestigial like 4 regulates the adipogenesis of classical brown adipose tissue
Authors: Zhou Pingzhu , Kessinger Chase W. , Gu Fei , Davenport Amanda , King Justin S. , Wang Genyu , Negron Steven G. , Deplancke Bart , Pu William T. , Lin Zhiqiang
Published: July 2024

Brown adipose tissue (BAT) is mammals’ primary non-shivering thermogenesis organ, and the molecular mechanisms regulating BAT growth and adipogenesis are largely unknown. The Hippo-YAP pathway has been well-known for controlling organ size, and Vestigial like 4 (VGLL4) is a transcriptional regulator that modulates the Hippo-YAP pathway by competing against YAP for binding to TEAD proteins. In this study, we dissected the function of VGLL4 in regulating BAT development. We generated a conventionalVgll4mutant mouse line, in which the two Tondu (TDU) domains of VGLL4 were disrupted. We found that deletion of the TDU domains of VGLL4 resulted in perinatal lethality and paucity of the interscapular BAT. Histological and magnetic resonance imaging studies confirmed that the adipogenesis of BAT was impaired inVgll4mutants. Adeno-associated virus (AAV) mediated, brown adipocyte-specific overexpression of VGLL4 increased BAT volume and protected the adult male mice from acute cold stress. Genomic studies suggest that VGLL4/TEAD1 complex directly regulates the myogenic and adipogenic gene expression programs of BAT. In conclusion, our data identify VGLL4 as a previously unrecognized adipogenesis factor that regulates classical BAT development.
Clinical implication of time of stroke among post stroke survivors from eastern India: A circadian perspective
Authors: Sadhukhan Dipanwita , Roy Arunima , Banerjee Tapas Kumar , Krishnan Prasad , Maitra Piyali Sen , Mukherjee Joydeep , Ghosh Kartick Chandra , Hui Subhra Prakash , Biswas Arindam
Published: July 2024

Introduction

The circadian variation in stroke occurrence is a well-documented phenomenon. However, the circadian effect on stroke outcome, particularly on post-stroke cognition, is not yet been fully elucidated.

Aims and objective

We aim to evaluate the influence of diurnal variation of stroke onset upon post-stroke cognition and development of post-stroke depression.

Materials and Methods

Based on 4-hourly time period of stroke occurrence, 249 recruited cohorts were categorized into 6 groups. Several clinical and cognitive parameters were compared among the groups. Then, the mRNA expression of core clock genes in Peripheral Blood Mononuclear Cells were quantified and correlated with post stroke outcome among 24 acute phase cases with day-time or night-time stroke occurrence. Furthermore, the genetic susceptibility towards higher number of cases in morning were examined by genotypingCLOCK(rs1801260T/C, rs4580704G/C) andCRY2(rs2292912C/G) genes variants in cases and 292 controls.

Results and conclusion

Among the six subgroups, the subgroup-1 represents the nocturnal-onset stroke cases; they were identified to have higher NIHSS score (12.2±5.67) at the time of admission than other subgroups (8.73±5.92). In the same cohort, more number of diabetic individuals with higher fasting blood sugar level (186.57±93.40) was also observed. After 6 months, those with nocturnal-onset stroke had higher prevalence of language impairment and depression score. A significant decrease in mRNA level ofBMAL1andCRY1genes correlated with raw score for language and depression; data in nocturnal onset cases further established our observation. However, the higher incidence of stroke in day time did not reveal any genetic correlation.
A study of the visualization of artificial intelligence applications in chronic kidney disease in the literature over the last 20 years
Authors: Li Yudi , Ding Ying , Xu Yan , Meng Haoji , Wu Hongji , Li Donglin , Hu Yibo
Published: July 2024

Chronic kidney disease (CKD) is a global public health problem characterized by persistent kidney damage or loss of kidney function. Previously, the diagnosis of CKD has mainly relied on serum creatinine and estimation of the glomerular filtration rate. However, with the development and progress of artificial intelligence (AI), AI has played different roles in various fields, such as early diagnosis, progression prediction, prediction of associated risk factors, and drug safety and efficacy evaluation. Therefore, research related to the application of AI in the field of CKD has become a hot topic at present. Therefore, this study adopts a bibliometric approach to study and analyze the development and evolution patterns and research hotspots of AI-CKD. English publications related to the field between January 1, 2004, and June 27, 2024, were extracted from the Web of Science Core Collection database. The research hotspots and trends of AI-CKD were analyzed at multiple levels, including publication trends, authors, institutions, countries, references and keywords, using VOSviewer and CiteSpace. The results showed that a total of 203 publications on AI-CKD were included in the study, of which Barbieri Carlo from the University of Milan, Italy, had the highest number of publications (NP=5) and had a high academic impact (H-Index=5), while the USA and its institution, the Mayo Clinic, were the publications. The USA and its Mayo Clinic are the countries and institutions with the highest number of publications, and China is the country with the second highest number of publications, with three institutions attributed to China among the top five institutions. Germany’s institution, Fresenius Medical Care, has the highest academic impact (H-index=6). Keyword analysis yielded artificial intelligence, chronic kidney disease, machine learning, prediction model, risk, deep learning, and other keywords with high frequency, and cluster analysis based on the timeline yielded a total of 8 machine learning, deep learning, retinal microvascular abnormality, renal failure, Bayesian network, anemia, bone disease, and allograft nephropathology clusters. This study provides a comprehensive overview of the current state of research and global frontiers of AI-CKD through bibliometric analysis. These findings can provide a valuable reference and guidance for researchers.
Memory B cell proliferation drives differences in neutralising responses between ChAdOx1 and BNT162b2 SARS-CoV-2 vaccines
Authors: Hodgson David , Liu Yi , Carolan Louise , Mahanty Siddhartha , Subbarao Kanta , Sullivan Sheena G. , Fox Annette , Kucharski Adam
Published: July 2024

Vaccination against COVID-19 has been pivotal in reducing the global burden of the disease. However, Phase III trial results and observational studies underscore differences in efficacy across vaccine technologies and dosing regimens. Notably, mRNA vaccines have exhibited superior effectiveness compared to Adenovirus (AdV) vaccines, especially with extended dosing intervals. Using in-host mechanistic modelling, this study elucidates these variations and unravels the biological mechanisms shaping the immune responses at the cellular level. We used data on the change in memory B cells, plasmablasts, and antibody titres after the second dose of a COVID-19 vaccine for Australian healthcare workers. Alongside this dataset, we constructed a kinetic model of humoral immunity which jointly captured the dynamics of multiple immune markers, and integrated hierarchical effects into this kinetics model, including age, dosing schedule, and vaccine type. Our analysis estimated that mRNA vaccines induced 2.1 times higher memory B cell proliferation than AdV vaccines after adjusting for age, interval between doses and priming dose. Additionally, extending the duration between the second vaccine dose and priming dose beyond 28 days boosted neutralising antibody production per plasmablast concentration by 30%. We also found that antibody responses after the second dose were more persistent when mRNA vaccines were used over AdV vaccines and for longer dosing regimens. Reconstructing in-host kinetics in response to vaccination could help optimise vaccine dosing regimens, improve vaccine efficacy in different population groups, and inform the design of future vaccines for enhanced protection against emerging pathogens.

SIGNIFICANCE STATEMENT

There are differences in vaccine efficacy across different SARS-CoV-2 vaccine technologies and dosing regimens. Using an in-host mechanistic model that describes antibody production fitting to in-host immune markers, we found that mRNA vaccines are twice as effective at stimulating memory B cell proliferation when compared to AdVs vaccines and that a longer time between the second vaccine dose and priming dose increases the neutralising antibody production per plasmablast concentration. These findings disentangle the effect of vaccine type and time since the priming dose, aiding in the understanding of immune responses to SARS-CoV-2 vaccination.
Artificial Intelligence Aided Ultrasound Detection of DDH: A Scoping Review Protocol
Authors: Yonis Rusul , Perry Daniel , Bowness James S , Khattak Mohammed , Hall Natalie
Published: July 2024

Background

Ultrasound imaging plays a pivotal role in the diagnosis and monitoring of developmental dysplasia of the hip (DDH). However, this step requires a formal referral to the radiology department for an ultrasound by an expert radiologist or sonographer. This process can delay diagnosis and treatment initiation due to long wait times caused by the high demand on NHS services.

In recent years, there has been a growing interest in leveraging artificial intelligence (AI) in ultrasound imaging. AI has potential to assist in image acquisition and interpretation, to inform clinical decision-making. Further benefits may include improved accuracy, efficiency, and consistency in diagnosis, ultimately leading to better patient outcomes.

This scoping review aims to review the evidence for AI to support ultrasound detection of DDH, including reviewing the methodologies employed, the accuracy and utility of algorithms, challenges and opportunities for clinical translation, and requirements for future research.

Methods

We will conduct a comprehensive search of the literature using multiple databases, including ACM Digital Library, EMBASE, OVID MEDLINE, PUBMED, COCHRANE Library, CINAHL, and IEEE Explore. These databases cover a wide range of academic disciplines, including computer science, and medical sciences, ensuring thorough coverage of relevant studies related to artificial intelligence (AI) in ultrasound for developmental dysplasia of the hip (DDH).

In addition, we will explore the International Committee of Medical Journal Editors (ICMJE) approved clinical trial registries and the World Health Organization (WHO) clinical trials registry to identify ongoing or completed studies in this field. This will capture relevant research that may not yet be published in peer-reviewed journals.

To supplement the research databases, we will search the websites of international societies in relevant fields, such as the British Society of Children’s Orthopaedic Surgery (BSCOS) and Paediatric Orthopaedic Society of North America (POSNA).

As AI has a strong commercial interest, we will review product information and publicly available evidence from EXO Imaging (https://www.exo.inc), a commercial company with a known interest in this field and an established AI aided US device.

Discussion

This scoping review represents the first comprehensive attempt to gather the available evidence on the application of AI in ultrasound imaging for the diagnosis of DDH. By systematically reviewing and synthesizing a diverse range of studies, we aim to provide an overview of the current state of the art in this emerging field, identify gaps in the literature, and inform future research.
Societal impact: leveraging operational excellence in the Iowa prison industries
Authors: Bumblauskas Dan , Guay Russell P. , Forbes Steve
Published: July 2024

Purpose

Prisons can utilize effective business process, operations management and continuous improvement techniques to provide an opportunity to support the rehabilitation of inmates. The purpose of this paper is to analyze the Iowa Prison Industries (IPI) work training program offered for incarcerated individuals under the supervision of the Iowa Department of Corrections (IDOC).

Design/methodology/approach

The IPI developed an Operational Excellence (OpEx) apprenticeship program that has worked with approximately 800 incarcerated “associates” to help them acquire skills necessary to obtain gainful employment upon release. This includes skills and belt level assessment in Lean Six Sigma as well as 6S/5S events and training. These techniques have been deployed by 22 teams at seven locations across the state of Iowa (USA). These sites have established objectives and goals and provided significant security-related benefits in the correctional industries environment.

Findings

Findings and success outcomes have been encouraging as those who completed the IPI apprenticeship program had lower recidivism, higher wages and more employability compared to the general prison population.

Social implications

The rehabilitation of incarcerated individuals is critical to society. This novel and unique case study reviews one approach to providing work and life skills (such as esteem-building professional and personal skill sets) to support this process within the prison system.

Originality/value

This OpEx program has provided numerous benefits to both IPI and the incarcerated individuals. We feel that these findings could be beneficial to other correctional institutions and better prepare more inmates for a successful return to the workforce and to society.