bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unified synthesis of NOPQ and STUV rings of brevisulcenal-F
Authors: Kawamurara Sho , Toriyama Kanako , Umeno Keitaro , Yasuno Yoko , Satake Masayuki , Oishi Tohru 
Published: September 2024

Abstract
The unified synthesis of the NOPQ and STUV rings of brevisulcenal-F was achieved from a common intermediate based on a convergent strategy via 2-ring construction. The STUV ring was synthesized via radical reduction of an O,S-acetal, and the NOPQ ring was constructed via ring expansion giving a 7-membered ring ketone, methylation of an O,S-acetal, and introduction of the cis-1,2-diol moiety at C60–C61.
A non-genetic model of vascular shunts informs on the cellular mechanisms of formation and resolution of arteriovenous malformations
Authors: Ouarné Marie , Pena Andreia , Ramalho Daniela , Conchinha Nadine V , Costa Tiago , Enjalbert Romain , Figueiredo Ana M , Saraiva Marta Pimentel , Carvalho Yulia , Bernabeu Miguel O , Henao Misikova Lenka , Oh S Paul , Franco Cláudio A 
Published: September 2024

Abstract

Aims
Arteriovenous malformations (AVMs), a disorder characterized by direct shunts between arteries and veins, are associated with genetic mutations. However, the mechanisms leading to AV shunt formation and how shunts can be reverted are poorly understood.

Methods and results
Here, we report that oxygen-induced retinopathy (OIR) protocol leads to the consistent and stereotypical formation of AV shunts in non-genetically altered mice. OIR-induced AV shunts show all the canonical markers of AVMs. Genetic and pharmacological interventions demonstrated that changes in the volume of venous endothelial cells (EC)—hypertrophic venous cells—are the initiating step promoting AV shunt formation, whilst EC proliferation or migration played minor roles. Inhibition of the mTOR pathway prevents pathological increases in EC volume and significantly reduces the formation of AV shunts. Importantly, we demonstrate that ALK1 signalling cell-autonomously regulates EC volume in pro-angiogenic conditions, establishing a link with hereditary haemorrhagic telangiectasia-related AVMs. Finally, we demonstrate that a combination of EC volume control and EC migration is associated with the regression of AV shunts.

Conclusion
Our findings highlight that an increase in the EC volume is the key mechanism driving the initial stages of AV shunt formation, leading to asymmetric capillary diameters. Based on our results, we propose a coherent and unifying timeline leading to the fast conversion of a capillary vessel into an AV shunt. Our data advocate for further investigation into the mechanisms regulating EC volume in health and disease as a way to identify therapeutic approaches to prevent and revert AVMs.
A case report: pitfalls in antibacterial therapy with rifampicin for mechanical valve endocarditis—the king of drug interactions
Authors: Honda Ryosuke , Akazawa Yusuke , Inoue Katsuji , Higaki Takashi , Yamaguchi Osamu 
Published: September 2024

Abstract

Background
Rifampicin is a strong inducer of the hepatic cytochrome P450 (CYP) family and is known to interact with many clinical drugs. However, to our knowledge, no case of worsening heart failure (HF) due to the interaction between rifampicin and HF drugs has been reported.

Case summary
A 32-year-old female, who had undergone intracardiac repair for an incomplete atrioventricular septal defect with dextrocardia and prosthetic valve replacements for right and left atrioventricular valve regurgitation, presented as an outpatient. Her medications included tolvaptan 15 mg and warfarin 1.25 mg. She had a slight fever and Osler nodes at her fingers. Blood culture bottles grew methicillin-resistant Staphylococcus epidermidis, and several vegetations were observed on the right atrioventricular mechanical valve with a transoesophageal echocardiogram. She was diagnosed with prosthetic valve endocarditis and treated with antibiotic agents including rifampicin. After a week, she developed systemic oedema and had a marked decrease in prothrombin time–international normalized ratio (PT-INR). Rifampicin was promptly discontinued due to a strong suspicion of a drug–drug interaction. Consequently, both her congestion and the PT-INR stabilized, and she was discharged after 8 weeks of antibiotic treatment.

Discussion
The introduction of rifampicin induces CYP family members such as CYP3A4 and CYP2C9. Warfarin is metabolized by CYP2C9 and tolvaptan is also metabolized by CYP3A4, resulting in a notable reduction of their blood levels when co-administered with rifampicin. The clinical challenges arising from interactions between HF drugs and rifampicin can be categorized into two main groups: worsening HF and thrombotic complications. Clinicians should remain vigilant and informed about these potential issues.
Prevalence of adrenal rest tumors and course of gonadal dysfunction in a clinical sample of men with congenital adrenal hyperplasia: a longitudinal analysis over 10 years
Authors: Auer Matthias K , Büyükerzurmulu Duygu , Lottspeich Christian , Bidlingmaier Martin , Rieger Eva , Nowotny Hanna , Tschaidse Lea , Auchus Richard J , Reisch Nicole 
Published: September 2024

Abstract

Background
Subfertility is prevalent in men with classic 21-hydroxylase deficiency (21OHD). We sought to characterize the long-term evolution of their gonadal function.

Methods
Retrospective longitudinal single-center study in 27 men (11 with testicular adrenal rest tissue [TART]), median observation period 12 years, testosterone (T), 11-oxygenated androgens, gonadotropins, and inhibin B measurement at each time point.

Results
T concentrations were below the normal range (n.s.) in 43.2% (no TART) and 54.6% (TART) per patient. After accounting for body mass index, sex hormone-binding globulin, and age, men with TART exhibited higher T (14.0 ± 0.80 nmol/L) than those without (11.9 ± 0.71 nmol/L). During the observation period, T levels rose in both groups but more in men with TART (from 10.1 ± 1.1 to 17.3 ± 1.9 nmol/L vs 10.3 ± 1.0 to 12.8 ± 1.9 nmol/L); this was accompanied by rising luteinizing hormone and diminishing hydrocortisone equivalent dosages (TART: from 38.1 ± 3.2 to 35.1 ± 1.8 mg/d; vs no TART: 28.8 ± 2.7 to 28.1 ± 1.6 mg/d) without correlation with any markers of adrenal androgen control. Inhibin B declined in men with large TART over time while TART status remained stable.

Conclusion
T levels below the normal range are frequent in men with 21OHD, regardless of TART, but change little over time. Besides adrenal androgen control gonadal axis suppression from supraphysiological glucocorticoid dosages needs to be considered. While our results do not endorse regular screening for alterations in TART status among adults, Sertoli cell function should be monitored in men with large TART.
Poly-ether-ether-ketone versus dead-soft coaxial bonded retainers: a randomized clinical trial. Part 2: periodontal health and microbial biofilm assessment
Authors: Jasim Esraa Salman , Kadhum Ammar Salim 
Published: September 2024

Abstract

Background
Retainers have the potential to detrimentally impact periodontal health and contribute to tooth decay.

Objectives
To investigate periodontal health and bacterial biofilm related to Poly-ether-ether-ketone (PEEK) fixed retainers as compared to Dead-soft coaxial fixed retainer (DSC).

Trial design
A two-arm parallel groups single-centre randomized clinical trial.

Methods
The trial included patients whose orthodontic treatment was completed and required retainers. Participants were randomly assigned into two retainer groups: PEEK retainers, prepared by computer-aided design and manufacturing into 0.8 mm wire form, and DSC retainers. The objectives included assessing periodontal health through plaque accumulation index (PI), bleeding on probing (BOP), periodontal pocket depth (PPD), gingival index (GI), calculus index (CI), and alveolar bone height (ABH) assessment. Biofilm assessment involved bacteriological screening of aerobic, facultative anaerobic, mutans streptococci, and lactobacilli. The periodontal indices and microbiological screening as well as were assessed at the debonding stage (T0), 1-month (T1), 3-month (T3), and 6-month (T6) after the commencement of the trial, except for the ABH, which was recorded using periapical radiograph at T0 and T6.

Blinding
Single blinding of participants in addition to the bacteriological specialist.

Results
Initially, the trial enrolled 46 participants, aged between 12 and 28 years, and were randomly assigned to two groups, with 23 participants in each group. Subsequently, one participant withdrew from the trial, resulting in a total of 45 participants whose data were analysed. Assessment of the periodontal indices, excluding the CI (P = .480), revealed statistically but not clinically significant differences between groups after 6-month of retention (P = .016 of PI, P = .020 of BOP, P = .05 of PPD, and P = .01 of GI). There was slight plaque accumulation, normal PPD (approximately 1 mm), healthy to mild gingivitis with a GI of less than 1 and BOP was around 10%. Concerning the ABH, there was a noticeable reduction in its score after 6 months, particularly in the PEEK group, although the difference was not statistically significant (P = .102). Furthermore, the bacteriological viable count did not show any significant difference between the groups during the recall visits.

Harms
There have been no reported negative consequences.

Limitations
Blinding the assessor of periodontal indices was not feasible due to the nature of the intervention. The trial follow-up duration was limited.

Conclusions
Both the PEEK and DSC retainers have comparable impacts on periodontal health and bacterial accumulation and composition during the retention period.

Trial registration
NCT05557136.
Pharmacokinetics of anti-TB drugs in children and adolescents with drug-resistant TB: a multicentre observational study from India
Authors: Agibothu Kupparam Hemanth Kumar , Shah Ira , Chandrasekaran Padmapriyadarsini , Mane Sushant , Sharma Sangeeta , Thangavelu Bharathi Raja , Vilvamani Sudha , Annavi Vijayakumar , Mahalingam Santhana Mahalingam , Thiruvengadam Kannan , Navaneethapandian Poorna Gangadevi , Gandhi Srushti , Poojari Vishrutha , Nalwalla Zahabiya , Oswal Vikas , Giridharan Prathiksha , Babu Sarath Balaji , Rathinam Sridhar , Frederick Asha , Mankar Shubhangi , Jeyakumar Shanmugam Murugaiha 
Published: September 2024

Abstract

Background
Drug-resistant tuberculosis (DR-TB) is one of the challenging forms of TB to treat, not only in adults but also in children and adolescents. Further, there is a void in the treatment strategy exclusively for children due to various reasons, including paucity of pharmacokinetic (PK) data on anti-TB drugs across the globe. In this context, the present study aimed at assessing the PK of some of the anti-TB drugs used in DR-TB treatment regimens.

Method
A multicentre observational study was conducted among DR-TB children and adolescents (n = 200) aged 1–18 years (median: 12 years; IQR: 9–14) treated under programmatic settings in India. Steady-state PK (intensive: n = 89; and sparse: n = 111) evaluation of moxifloxacin, levofloxacin, cycloserine, ethionamide, rifampicin, isoniazid and pyrazinamide was carried out by measuring plasma levels using HPLC methods.

Results
In the study population, the frequency of achieving peak plasma concentrations ranged between 13% (for rifampicin) to 82% (for pyrazinamide), whereas the frequency of suboptimal peak concentration for pyrazinamide, cycloserine, moxifloxacin, levofloxacin and rifampicin was 15%, 19%, 29%, 41% and 74%, respectively. Further, the frequency of supratherapeutic levels among patients varied between 3% for pyrazinamide and 60% for isoniazid. In the below-12 years age category, the median plasma maximum concentration and 12 h exposure of moxifloxacin were significantly lower than that of the above-12 years category despite similar weight-adjusted dosing.

Conclusions
Age significantly impacted the plasma concentration and exposure of moxifloxacin. The observed frequencies of suboptimal and supratherapeutic concentrations underscore the necessity for dose optimization and therapeutic drug monitoring in children and adolescents undergoing DR-TB treatment.
Nocturnal activity and forestry-urban dispersal of phlebotomine sand flies (Diptera: Psychodidae) from an ecotourism park in Amazonian Brazil
Authors: Neves Danielly Mota , Sánchez Uzcátegui Yetsenia del Valle , Silveira Fernando Tobias , Vasconcelos dos Santos Thiago 
Published: September 2024

Abstract
Phlebotomine sand flies are insects of notorious importance in public health, mainly due to their involvement in the transmission of Leishmania protozoa. Their flight activity occurs predominantly in the twilight/night period, being stimulated mainly by the need to search for food and reproduction. Despite being naturally wild, some species are able to invade anthropized environments. Present work aimed to assess the nocturnal activity and forestry-urban dispersal of phlebotomine sand flies from an ecotourism park in Belém, Amazonian Brazil. The study area comprised a horizontal transect, extending from a forest park to the neighboring urban environment, in Belém. Sampling was conducted with night-operating light traps. Nocturnal activity was assessed through time-set captures with a collection bottle rotator in the forest environment. Dispersal was assessed through captures carried out along the transect, starting from the forest edge (0 m), extending to the urban environment (50–200 m), phlebotomine sand flies were identified. Abundance, richness, diversity, and sampling sufficiency were estimated. Fourteen species were recorded in the surveyed environments, with Nyssomyia antunesi, Trichophoromyia brachipyga, and Trichophoromyia ubiquitalis being the most abundant. Nocturnal activity behavior of Ny. antunesi occurred between 8 PM and 4 AM while that of Th. brachipyga and Th. ubiquitalis occurred between 2 AM and 6 AM. In the urban environment, the 150 m site presented the highest abundance. Bichromomyia flaviscutellata was sampled in all sites. Gravid females of Pressatia choti and Bi. flaviscutellata were sampled in the urban environment. Putative differential activity between the species herein assessed and their urban dispersal observed are worthy of note, adding data for supporting vector surveillance at a local scale.
Tracking community outreach and engagement activities among National Cancer Institute-designated cancer centers
Authors: Burus Todd , McAfee Caree R , Hull Pamela C , Leader Amy E , McNair Christopher 
Published: September 2024

Abstract
The National Cancer Institute’s (NCI) Cancer Center Support Grant mandates that NCI-designated cancer centers establish a Community Outreach and Engagement (COE) component to help direct efforts at reducing cancer burden within their catchment areas. Despite the critical role of COE offices, little is known about how they track and evaluate outreach activities and outcomes. We gathered information on current practices from representatives of 40 out of 65 COE offices using an online survey. Although nearly all responding centers (97.5%) tracked COE activities, no consensus existed on resources used, and satisfaction with current solutions was mixed (51.0% not satisfied). Respondents expressed need for a centralized, standardized, and comprehensive tracking solution to capture outreach events and external partnerships, automate report generation, and ensure alignment with COE aims. This study highlights challenges COE offices face with resource limitations and a heterogeneity of activities to track, as well as the need for a standard evaluation framework.
Replacing middle colic artery arising from the splenic artery—an arterial variety in a patient undergoing total pancreatoduodenectomy
Authors: Karitnig Robert , Margreiter Christian , Wagner Doris , Wienerroither Valerie Fanny , Lederer Andri , Hau Hans Michael , Kornprat Peter , Talakic Emina , Sucher Robert 
Published: September 2024

Abstract
Knowledge of variations in arterial vascular supply is crucial in HPB and general surgery. Although the arterial configuration of the coeliac trunk and the superior mesenteric artery had been investigated, there are still arterial branching patterns to be described. We herein present the case of an 84-year-old male patient who underwent total pancreatectomy due to a not specified pancreas head tumor with a replacing right hepatic artery according to Michel’s classification III and a replacing middle colic artery arising from the splenic artery and running on the ventral side of the pancreas. To the best of our knowledge, this arterial branching pattern has never been described so far. In this case, two arterial variations had been presented with a type III arterial supply according to Michel’s classification, and a replacing middle colic artery arising from the SA.
Interval robotic cholecystoduodenal fistula repair and cholecystectomy for gallstone ileus: a case report
Authors: Agathis Alexandra Z , Ray Keval , Sharma Bharti , Whittington Jennifer 
Published: September 2024

Abstract
Gallstone ileus is an uncommon pathology that often requires surgery in the acute setting to address the bowel obstruction, followed by definitive biliary management. Sparse literature cites the use of robotic technique in this setting. We present the case of an 86-year-old female with an independent functional status and a history of medically-managed cholecystitis, who previously declined cholecystectomy. Years later, she presented acutely with a small bowel obstruction secondary to gallstone ileus. At that time, she underwent a diagnostic laparoscopy, small laparotomy, and enterotomy for extraction of her gallstone. She returned 7 months later for an interval elective robotic-assisted cholecystectomy and repair of a cholecystoduodenal fistula. The duodenotomy was repaired in two layers with absorbable suture. Postoperatively, an upper gastrointestinal study showed normal passage of contrast without leakage. She recovered well, and shortly after returned to her baseline functional status.
COVID-19-induced changes in the workplace, psychosocial work environment and employee well-being: a longitudinal study
Authors: Kausto J , Airaksinen J , Oksanen T , Vahtera J , Kivimäki M , Ervasti J 
Published: September 2024

Abstract

Background
In many workplaces, the coronavirus disease 2019 pandemic changed work arrangements, but there is scarce longitudinal evidence on whether psychosocial work environment and employee well-being were affected.

Aims
To examine the psychosocial work environment and employee well-being before, during and after the pandemic in relation to pandemic-induced changes (working from home, change to other tasks and team reorganization).

Methods
Survey data from a cohort of 20 944 public sector employees in Finland were collected before (2016–2018), during (2020) and after the pandemic (2022). Multilevel linear and logistic regression was used to examine group differences between the before–during and during–after periods of the pandemic.

Results
Working from home was associated with a small but favourable change in worktime control, organizational justice and social capital (scale 1–5) during the pandemic and after the pandemic (marginal mean difference ranging from 0.02 to 0.09 with 95% confidence intervals [CIs] from 0.01 to 0.10). There was a post-pandemic increase in work time control, even among participants with a transfer into other tasks (0.11, 95% CI 0.07, 0.14) or team reorganization (0.06, 95% CI 0.02, 0.10). The decline in self-rated work ability (scale 0–10) before and during the pandemic was greater in those transferred into other tasks (−0.10, 95% CI −0.13, −0.06) than in those not (−0.05, 95% CI −0.06, −0.04).

Conclusions
Working from home during the pandemic was accompanied by small favourable changes in the psychosocial work environment during the pandemic, whereas transition to different tasks was associated with a decline in self-rated work ability.
A DNA-free and genotype-independent CRISPR/Cas9 system in soybean
Authors: Kuwabara Chikako , Miki Ryuji , Maruyama Nobuyuki , Yasui Masanori , Hamada Haruyasu , Nagira Yozo , Hirayama Yumiko , Ackley Wataru , Li Feng , Imai Ryozo , Taoka Naoaki , Yamada Tetsuya 
Published: September 2024

Abstract
Here, we report a smart genome editing system for soybean (Glycine max) using the in planta bombardment-ribonucleoprotein (iPB-RNP) method without introducing foreign DNA or requiring traditional tissue culture processes such as embryogenesis and organogenesis. Shoot apical meristem (SAM) of embryonic axes was used as the target tissue for genome editing because the SAM in soybean mature seeds has stem cells and specific cell layers that develop germ cells during the reproductive growth stage. In the iPB-RNP method, the RNP complex of the CRISPR/Cas9 system was directly delivered into SAM stem cells via particle bombardment, and genome-edited plants were generated from these SAMs. Soybean allergenic gene Gly m Bd 30K was targeted in this study. Many E0 (the first generation of genome-edited) plants in this experiment harbored mutant alleles at the targeted locus. Editing frequency of inducing mutations transmissible to the E1 generation was approximately 0.4% to 4.6% of all E0 plants utilized in various soybean varieties. Furthermore, simultaneous mutagenesis by iPB-RNP method was also successfully performed at other loci. Our results offer a practical approach for both plant regeneration and DNA-free genome editing achieved by delivering RNP into the SAM of dicotyledonous plants.
Chemokine receptor CXCR4 based positron emission tomography imaging in systemic sclerosis-related interstitial lung disease
Authors: Kopp Chirag Rajkumar , Sharma Shefali Khanna , Krishnaraju Venkata Subramanian , Sood Ashwani , Kumar Rajender , Sinha Anindita , Dhooria Sahajal , Singh Jagdeep , Anand Shashi , Minz Ranjana Walker , Dhir Varun , Jain Sanjay 
Published: September 2024

Abstract

Objective
To assess chemokine receptor CXCR4 expression in lung parenchyma and on peripheral immune cells in systemic sclerosis-related interstitial lung disease (SSc-ILD) patients.

Methods
SSc-ILD patients underwent 68Ga- CPCR4 Trifluoroacetate positron emission tomography (PET) scan, SUVmean in different lung regions and architecturally abnormal areas, and receiver operating characteristic (ROC) curves were analysed. CXCR4 expression on peripheral immune cells using flow cytometer was studied and correlated with the different lung regions. In addition, subset analysis of CXCR4 expression by clinical subset (early, progressive, stable), ILD pattern and anti-Scl-70 positivity were done.

Results
On PET, SSc-ILD patients showed higher median SUVmean uptake of CXCR4 in the whole lung (0.56; P &lt; 0.0001), different lung regions and architecturally abnormal areas than controls. The highest area under curve (AUC) was observed in dorsobasal regions (AUC-0.91; P &lt; 0.0001) and reticular with architecturally distorted areas (AUC-0.95; P &lt; 0.0001). The progressive subset had higher whole lung median SUVmean (0.73) than early (0.49; P &lt; 0.0001) and stable (0.45; P &lt; 0.0001) subsets, and AUC than early and stable subsets. Usual interstitial pneumonia pattern ILD showed higher CXCR4 uptake compared with non-specific interstitial pneumonia (P = 0.0032). Additionally, a trend for higher uptake was noted in anti-Scl70 positive patients as compared with anti-Scl70 negative ones. SSc-ILD patients had higher CD4+CXCR4+T cells (P = 0.0003) and CD8+CXCR4+T cells (P = 0.0013) and showed moderate to strong association on correlation with the lung parenchymal regions.

Conclusion
In SSc-ILD, CXCR4 expression is upregulated in both lung parenchyma and peripheral T cells, significantly in progressive and UIP subsets. CXCR4 expression is a potential tool for activity assessment and prognostication.