bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the risk of hypersensitivity reactions to iopromide differ by sex, race, or across regions/countries? An analysis of 152 233 patients from 4 observational studies and the company’s pharmacovigilance database
Authors: Endrikat Jan , Ullmann Alexander , Gerlinger Christoph , Bhatti Aasia , Lengsfeld Philipp , Michel Alexander
Published: September 2024

Objective

To analyse the potential impact of patients’ sex, race, and region/country on the risk of hypersensitivity reactions after intra-venous or intra-arterial administration of iopromide.

Methods

Two analyses were performed. (1) The “Phase-IV-Analysis” evaluated an integrated pooled database of 4 non-interventional studies. (2) The “GPV-Analysis” evaluated case reports from the company’s pharmacovigilance database. The Phase-IV-Analysis was a nested case–control analysis of patients who received an injection of iopromide 300/370 mg iodine/mL. Cases had typical/unequivocal HSRs as defined by the ACR Committee on Drugs and Contrast Media 2018. The global pharmacovigilance (GPV)-Analysis was based on HSR case reports in the company database. Exposure estimates were derived from sales/market research data.

Results

The Phase-IV-Analysis comprised 152 233 patients from 37 countries. In the full-analysis set 145 033, 59 412, and 146 649 patients were included in the sex, race, and region/country cohort, respectively. The GPV-Analysis was based on 78.72 million administrations for sex and 118.56 million administrations for region/country. No GPV exposure data by race were available. Sex: Phase-IV-Analysis: The HSR incidence was significantly higher for women (0.72%) vs men (0.55%) (P ≤ .0001). The unadjusted odds ratio (OR) was 1.3 (95% CI, 1.154-1.499), the adjusted OR was 1.156 (95% CI, 1.006-1.328) (P = .04). GPV-Analysis: Reporting rates were 0.0102% for women and 0.0075% for men (P < .0001). OR: 1.36 (95% CI, 1.3-1.43). Race: Phase-IV-Analysis: No significantly different HSR incidences for white (0.70%) and Asian (0.61%) patients (P = .3094) were detected. Region/country: Phase-IV-Analysis: The overall world HSR-incidence was 0.62%. Europe: 0.52%, Asia: 0.70%, United States: 0.75%, Germany: 0.51%, China: 0.41%, South Korea: 0.76%. GPV-Analysis: The overall world HSR-reporting rate was 0.015%, varying across regions/countries.

Conclusion

Women showed a slightly higher risk for HSRs than men. Impact of race was not found. HSR-reporting varied by region/country.

Advances in knowledge

Risk for HSRs was increased by female sex but not by race or region/country.
Theoretical and experimental studies on the effect of the 1,2-diketone group on geometry distortion for phenacene-type polycyclic aromatic compounds
Authors: Hamamoto Nobutsugu , Rakumitsu Kenta , Kusumoto Sotaro , Yokoyama Akihiro , Inokuchi Makoto
Published: September 2024

This paper addresses the geometry distortion of orthoquinone-containing phenacene-type compounds by comparing the structures of phenanthrene-9,10-dione, chrysene-5,6-dione, and picene-13,14-dione. Interestingly, the calculated geometry of chrysene-5,6-dione under the isolated state was drastically different from the experimental one observed by single-crystal X-ray analysis. Theoretical calculations suggested that the molecular geometry of the o-quinone derivatives was sensitive not only to the sterically intramolecular proximity between the carbonyl oxygen and the hydrogen atoms of the benzene rings but also to intermolecular interactions. The twist distortion affects properties such as oscillator strength and 1-electron transitions, for low-lying excited states.
Refocusing social work education on community work in Hong Kong: an urgent call
Authors: Cheung Johnson Chun-Sing
Published: September 2024

A dominant discourse in social work literature and textbooks is that community workers should take a proactive stance to pressure government officials to reform policy. Without any mission to downplay the political role of social work in the first place, the author of this paper argues that activist discourses from the 1970s are too old to inform contemporary struggles. In light of the neo-liberal, neo-managerial, post-colonial, and pan-political realities, antagonistic relationships between stakeholders in the community, politicians, opinion leaders, and the establishment have ushered in new-look community work in Hong Kong. Social work education on community development should undergo a transformation to help social work students reposition themselves in these chaotic times.
Significant low-temperature activity of tetragonal-type ZrO2-supported Ru catalysts for CO2 methanation
Authors: Sato Katsutoshi , Higuchi Hitomi , Nagaoka Katsutoshi
Published: September 2024

Conversion of CO2 with H2 to CH4 is a potential route for the utilization of CO2. Because CO2 methanation is an exothermic reaction, the equilibrium yield decreases with increasing temperature. A catalyst that exhibits high activity at low temperatures is thus highly desirable. We report here that a tetragonal-type ZrO2-supported Ru catalyst prepared by low-temperature calcination showed significant low-temperature activity for CO2 methanation. We surmise that an intermediate formate species formed over the tetragonal-type ZrO2 and enhanced the catalytic activity.
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

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

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

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

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

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

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

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

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

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

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

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

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

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 < 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 < 0.0001) and reticular with architecturally distorted areas (AUC-0.95; P < 0.0001). The progressive subset had higher whole lung median SUVmean (0.73) than early (0.49; P < 0.0001) and stable (0.45; P < 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.
Diagnostic accuracy of hip joint ultrasound for detection of calcium pyrophosphate deposition
Authors: Soto-Fajardo Carina , Carranza-Enríquez Fabián , Pichardo-Bahena Raúl , Clavijo-Cornejo Denise , Ilizaliturri-Sánchez Víctor Manuel , Flores-Ordoñez Paola , Ángeles-Acuña Abish , Solórzano-Flores Sinthia , Filippou Georgios , Sandoval Hugo , Pineda Carlos
Published: September 2024

Objective

CPPD disease is a chronic and disabling arthropathy. US has been shown to be a tool with high sensitivity and specificity for the diagnosis of CPPD disease, but its value at the hip joint has not yet been determined. Therefore, our objective was to evaluate the diagnostic accuracy of US for the identification of CPP crystals in the hip joint as compared with histopathology.

Methods

Diagnostic test study involving patients over 50 years of age with osteoarthritis, scheduled for hip replacement surgery. US was performed on the affected hip. Acetabular fibrocartilage (FC) and hyaline cartilage (HC) of the femoral head were assessed, and a dichotomous score was used for the presence/absence of CPP crystals. SF was obtained from the affected hip and examined using polarized light microscopy. Histopathological examination was performed by an experienced pathologist in search of CPP crystals in FC and HC samples.

Results

One hundred patients were enrolled, of whom 62% were found to have hyperechoic areas suggestive of CPP deposition on US examination. Pathological evaluation revealed a prevalence of 61% of CPP crystals. The sensitivity, specificity and the positive predictive and the negative predictive values were 90%, 82%, 89%, and 84%, respectively. The area under the curve for US compared with histopathology for the diagnosis of hip CPPD was 0.86 (95% CI: 0.78–0.94).

Conclusion

US is a valid imaging modality with good diagnostic accuracy for the detection of hip CPPD.
Increased Sensitivity to Effort and Perception of Effort in People with Schizophrenia
Authors: Culbreth Adam J , Chib Vikram S , Riaz Safa S , Manohar Sanjay G , Husain Masud , Waltz James A , Gold James M
Published: September 2024

Objective

Motivational deficits in schizophrenia are proposed to be attributable in part to abnormal effort-cost computations, calculations weighing the costs vs. the benefits of actions. Several reports have shown that people with schizophrenia display a reduced willingness to exert effort for monetary rewards when compared to controls. The primary goal of the current study was to further characterize reduced willingness to exert effort in schizophrenia by determining whether reduced willingness reflects (1) reduced sensitivity to reward, (2) increased sensitivity to effort, or (3) a combination of both.

Design

We assessed effort-cost decision-making in 30 controls and 30 people with schizophrenia, using 2 separate experimental tasks. Critically, one paradigm allowed for independent estimation of effects of reward and effort sensitivity on choice behavior. The other task isolated effort sensitivity by measuring effort in the absence of reward. Clinical interviews and self-report questionnaires were administered to people with schizophrenia to determine negative symptom severity.

Results

Across both tasks, we found evidence for reduced willingness to exert effort in people with schizophrenia compared to controls. Further, in both paradigms reduced willingness to exert effort was driven by increased sensitivity to effort in people with schizophrenia compared to controls. In contrast, measures of reward sensitivity did not significantly differ between groups. Surprisingly, we did not find correlations between task variables and measures of negative symptom severity.

Conclusions and Relevance

These findings further specify prior work by identifying a specific contributory role for increased effort sensitivity in effort-cost decision-making deficits in schizophrenia.
The neurocranium of Potamotrygonidae: morphology and phylogenetic significance
Authors: Araújo Marcus V G , Vaz Diego F B , Medeiros Jade , de Lima Arthur , Rosa Ricardo S , Loboda Thiago S , da Silva João Paulo C B
Published: September 2024

The family Potamotrygonidae is part of the Neotropical ichthyofauna and has the largest diversity of freshwater elasmobranchs in the world. The neurocranium in Potamotrygonidae is an elongated and dorsoventrally flattened structure that articulates anterolaterally with the anterior portion of the propterygium, posteriorly with the sinarcual, and posterolaterally with the hyomandibula. This anatomical structure is comparatively described in Potamotrygonidae in an effort to reveal new phylogenetically relevant characters. Additionally, a new genus-level phylogeny of the family is proposed herein based on 60 novel morphological characters. The subfamily Potamotrygoninae, whose monophyly is well sustained by previous studies, is further supported herein by a variable number of cranial synapomorphies (up to 17), depending on the optimization adopted. Furthermore, we also recovered Potamotrygon and Plesiotrygon as consecutive sister-groups to a clade including Heliotrygon and Paratrygon. The neurocranium of potamotrygonids and its anatomical variation is also discussed in the context of previous morphological and molecular phylogenies of Neotropical freshwater stingrays.
Transcranial Direct Current Stimulation Reduces Pressure Pain Sensitivity in Patients With Noncancer Chronic Pain
Authors: Zolezzi Daniela M. , Kold Sebastian , Brock Christina , Jensen Anne Birthe Helweg , Jensen Sarah Thorius , Larsen Isabelle Myriam , Olesen Søren Schou , Mørch Carsten Dahl , Drewes Asbjørn Mohr , Graven-Nielsen Thomas
Published: September 2024

Objectives:

Noncancer chronic pain is a clinical challenge because pharmacological treatment often fails to relieve pain. Transcranial direct current stimulation (tDCS) is a treatment that could have the potential for pain relief and improvement in quality of life. However, there is a lack of clinical trials evaluating the effects of tDCS on the pain system. The aim of the present study was to evaluate the effect of 5 days of anodal tDCS treatment on the pain system in patients with chronic noncancer pain using quantitative sensory testing and quality of life questionnaires: (1) Brief Pain Inventory-short form, (2) European Organization for Research and Treatment of Life Questionnaire-C30, and (3) Hospital Anxiety Depression Scale.

Methods:

Eleven patients with noncancer chronic pain (51 ± 13.6 y old, 5M) participated in the study. Anodal tDCS was applied for 5 consecutive days, followed by sham stimulation after a washout period of at least 2 weeks. Pressure pain thresholds and pain tolerance thresholds (PTT) were assessed in different body regions on days 1 and 5.

Results:

Anodal tDCS appeared to maintain PTT at C5 (clavicle) on day 5, but sham stimulation decreased PTT (P = 0.007). In addition, anodal tDCS increased PTT compared with sham at day 5 at Th10 ventral dermatomes (P = 0.014). Both anodal and sham tDCS decreased the Brief Pain Inventory-short form total and interference scores, and the European Organization for Research and Treatment of Life Questionnaire-C30 fatigue score, but no interaction effect was observed.

Conclusion:

This study adds to the evidence in the literature that tDCS may be a potential therapeutic tool for the management of noncancer chronic pain.
Changes in Intra- and Cross-hemispheric Directed Functional Connectivity in the Electroencephalographic Signals during Propofol-induced Loss of Consciousness
Authors: Troyas Carla , Ostertag Julian , Schneider Gerhard , García Paul S. , Sleigh Jamie W. , Kreuzer Matthias
Published: September 2024

Background:

Numerous, sometimes conflicting, changes in brain functional connectivity have been associated with the transition from wakefulness to unresponsiveness at induction of general anesthesia. However, relatively few studies have looked at the detailed time evolution of the transition, for different electroencephalogram (EEG) frequency bands, and in the clinical scenario of surgical patients undergoing general anesthesia.

Methods:

The authors investigated the changes in the frontal and frontoparietal directed and undirected functional connectivity to multichannel EEG data recorded from 29 adult male surgical patients undergoing propofol-induced loss of consciousness during induction of anesthesia. Directed functional connectivity was estimated using bivariate frequency domain Granger causality, and undirected connectivity was assessed using EEG coherence.

Results:

Around the point of loss of consciousness, local frontal, interhemispheric frontal, and frontoparietal feedback and feedforward Granger causality all decreased between 31% and 51.5% in the delta band (median [interquartile range] for local frontal, 0.14 [0.08, 0.27] to 0.08 [0.06, 0.12]; P = 0.02). After a lag of a few minutes, Granger causality markedly increased in the gamma and beta bands for local frontal (0.03 [0.02, 0.07] to 0.09 [0.07, 0.11]; P < 0.001) and long-distance cross-hemispheric frontoparietal feedback (0.02 [0.01, 0.04] to 0.07 [0.04, 0.09]; P < 0.001) and feedforward (0.02 [0.01, 0.04] to 0.03 [0.03, 0.04]; P = 0.01) coupling, but not for within-hemispheric frontoparietal feedback and feedforward. Frontal interhemispheric EEG coherence significantly decreased in the lower frequencies (f < 12 Hz) at loss of consciousness, while no significant increase for the beta and gamma bands was observed.

Conclusions:

Propofol-induced loss of consciousness in surgical patients is associated with a global breakdown in low-frequency directed functional connectivity, coupled with a high-frequency increase between closely located brain regions. At loss of consciousness, Granger causality shows more pronounced changes than coherence.
Corneal Layer Thickness Mapping With Optical Coherence Tomography in Different Stages Reveals Pathologic Processes of Keratoconus
Authors: Koh Shizuka , Inoue Ryota , Ambrósio Renato , Lopes Bernardo , Matsuo Risako , Maeno Sayo , Maeda Naoyuki , Kohji Nishida
Published: September 2024

Purpose:

The aim of this study was to characterize the corneal layer thickness profile in different stages of keratoconus (KC).

Methods:

Patients with clinical or subclinical KC without a history of contact lens use were retrospectively enrolled. We evaluated 164 eyes, including 69 clinical KC, 32 topographic KC (no clinical signs), 22 very asymmetric ectasia with normal topography and no clinical signs of ectasia (VAE-NT), and 41 control eyes. The corneal epithelial, stromal, and total thicknesses in a 10-mm diameter were evaluated using swept-source anterior segment optical coherence tomography.

Results:

The epithelial thickness in the control and VAE-NT groups was thicker inferiorly than superiorly. While epithelial thickness parameters between the VAE-NT and control groups did not differ, significant stromal thinning was observed in the paracentral inferior and midperipheral temporal areas. The epithelium in the topographic and clinical KC groups was thinner than that in the control and VAE-NT groups, with focal thinning of the epithelium in the inferior-temporal area. In clinical KC, stromal thinning increased mainly in the central and paracentral inferior/temporal areas. With KC progression, the thinnest epithelial points tended to be placed temporally and inferiorly.

Conclusions:

Corneal layer thickness mapping using swept-source optical coherence tomography in a 10-mm diameter cornea across various severities of KC, from very mild to advanced, revealed that epithelial and stromal thicknesses changed with KC severity and was involved in the pathogenesis of KC progression. Pathological changes in the stroma may precede those in the epithelium. Epithelial compensatory mechanisms in clinical and topographic KC may not have fully emerged in VAE-NT.
Impact of Acute Short-Term Hypobaric Hypoxia on Anterior Chamber Geometry
Authors: Xie Yuan , Sun Yunxiao , Shao Yaqi , Tian Jiaxing , Fu Yingdi , Yang Diya , Yang Yiquan , Cao Kai , Zhang Ye , Wang Huaizhou , Wang Guozhong , Wang Ningli
Published: September 2024

Précis:

Hypobaric hypoxia, the major environmental factor at high altitudes, has been observed to induce pupil miosis and widening of the anterior chamber angle. This environment may be safe for individuals with narrow angle and deserves further study.

Purpose:

This study aimed to quantify anterior chamber biometric parameters before and after acute short-term, effortless exposure to hypobaric hypoxia (HH) in healthy lowlanders using swept-source anterior segment optical coherence tomography (SS AS-OCT).

Methods:

This prospective study included 25 healthy young lowlanders (50 eyes) who underwent SS AS-OCT measurements and intraocular pressure (IOP) assessments under baseline sea-level conditions (T1). They were then passively exposed to simulated 4000 m above sea level for 3 hours and underwent acute mountain sickness (AMS) symptoms evaluation and IOP measurement after 2 hours exposure to HH (T2). Repeat SS AS-OCT measurements and IOP assessments were taken within 15 minutes after leaving the hypobaric chamber (T3). Anterior segment parameters including anterior chamber depth (ACD), lens vault (LV), angle opening distance (AOD500), trabecular-iris space area (TISA500), angle recess area (ARA500) at 500 μm from the scleral spur, iris curvature (IC), iris volume (IV), pupil diameter (PD), and central corneal thickness (CCT) were obtained through SS AS-OCT. These repeated measurements were compared using linear mixed model analysis.

Results:

In comparison to the sea level, both IOP (16.4±3.4 vs. 14.9±2.4 mm Hg, P=0.029) and PD (5.36±0.77 vs. 4.78±0.89 mm, P=0.001) significantly decreased after exposure to HH. Significant post-HH changes [mean difference (95% CI)] were observed in AOD500 [0.129 (0.006, 0.252), P=0.04], TISA500 [0.059 (0.008, 0.11), P=0.025], ARA500 [0.074 (0.008, 0.141), P=0.029], IV [1.623 (0.092, 3.154), P=0.038], and IC [−0.073 (−0.146, 0.001), P=0.047], whereas CCT, ACD, and LV remained stable. After adjusting for age, post-HH variations in AOD500 (Beta=0.553, 95% CI: 0.001, 1.105, P=0.048) and TISA500 (Beta=0.256, 95% CI: 0.02, 0.492, P=0.034) were associated with decreased IC but were not related to lowered arterial oxygen pressure or IV increase per millimeter of pupil miosis (IV/PD). These differences in anterior segment parameters were neither correlated with differences in IOP nor AMS.

Conclusions:

After short-term, effortless exposure to hypobaric hypoxia, pupil miosis occurred with widening of the anterior chamber angle and decreased IC. These changes in anterior chamber angle parameters were associated with decreased IC but did not correlate with the post-hypobaric variations in IV/PD, IOP, or AMS.
Chronic kidney disease and itch
Authors: Azimi Seyyede Zeinab , Lerner Ethan A.
Published: September 2024

Chronic kidney disease–associated pruritus (CKD-aP) is a prevalent and challenging symptom in patients with CKD and end-stage renal disease (ESRD). The aim of this review is to update existing evidence on the pathogenesis and treatments of pruritus in CKD and to shed light on areas that hold promise. The uncertain pathogenesis, and thus seemingly miscellaneous causes, identifies chronic itch as an important challenge in health care. A complex interaction of uremic toxin accumulation, micro and systemic inflammation, dysregulation of the opioid system, and mast cell activation may each contribute to the pathophysiology of CKD-aP. No highly satisfactory antipruritic therapeutics are available. Difelikefalin, considered to be a peripherally acting highly selective kappa-opioid receptor agonist, has been shown to have a positive impact on CKD-aP. Approved by the FDA in 2021 for intravenous administration, difelikefalin remains the most recent drug available. A developing area is that altered hemoglobin metabolism may lead to the activation of mas-related G protein–coupled receptors (MRGPRs). As this family of receptors is associated with itch, it is possible that drugs that target certain MRGPRs may be of future benefit in CKD-aP.
Comparing Endoscopic Treatment Modalities for Gastric Antral Vascular Ectasia
Authors: Gangwani Manesh Kumar , Haghbin Hossein , Hasan Fariha , Dillard Julia , Jaber Fouad , Dahiya Dushyant Singh , Ali Hassam , Kamal Faisal , Hayat Umar , Lee-Smith Wade , Sohail Amir , Inamdar Sumant , Aziz Muhammad , Adler Douglas G.
Published: September 2024

Objective:

Gastric antral vascular ectasia (GAVE) is characterized by vascular ectasias accounting for 4% of nonvariceal upper gastrointestinal bleeds, which can range from occult bleeds to severe acute upper gastrointestinal bleeding. In turn, GAVE can lead to severe morbidity and recurrent hospitalization. Current endoscopic treatments for GAVE include argon plasma coagulation (APC), endoscopic band ligation (EBL), and radiofrequency ablation. With this significant burden in mind, a systematic review and network meta-analysis were conducted to compare the efficacy and safety of various modalities in the treatment of GAVE.

Methods:

All studies that involved adults and children with endoscopic characteristics of GAVE undergoing treatment with APC, EBL, radiofrequency ablation, or a combination of 2 treatment modalities were included.

Results:

There was no statistical difference in the rate of adverse events and the number of red blood cell transfusions across all 3 groups (APC, EBL, and APC + EBL). However, statistical differences were noted for outcomes of bleeding recurrence, length of hospitalization, and change in hemoglobin status. EBL exhibited a significant decrease in bleeding recurrence when compared with APC. Moreover, shorter hospitalization stays were seen in APC + EBL and EBL groups compared with APC, and a beneficial change in hemoglobin status was also more often seen in APC + EBL and EBL groups compared with APC.

Conclusions:

Based on this study, EBL was found to have superior efficacy when compared with APC for the treatment of GAVE; however, there was no significant difference in rates of adverse events between APC, EBL, and combination therapy.