bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Genomic Landscape of FGFR3-Altered Urothelial Carcinoma and Treatment Outcomes with Erdafitinib: A Real-World Experience
Authors: Guercio Brendan J. , Sarfaty Michal , Teo Min Yuen , Ratna Neha , Duzgol Cihan , Funt Samuel A. , Lee Chung-Han , Aggen David H. , Regazzi Ashley M. , Chen Ziyu , Lattanzi Michael , Al-Ahmadie Hikmat A. , Brannon A. Rose , Shah Ronak , Chu Carissa , Lenis Andrew T. , Pietzak Eugene , Bochner Bernard H. , Berger Michael F. , Solit David B. , Rosenberg Jonathan E. , Bajorin Dean F. , Iyer Gopa
Published: September 2023

Purpose:

Erdafitinib is the only FDA-approved targeted therapy for FGFR2/3-altered metastatic urothelial cancer. We characterized the genetic landscape of FGFR-altered urothelial carcinoma and real-world clinical outcomes with erdafitinib, including on-treatment genomic evolution.

Experimental Design:

Prospectively collected clinical data were integrated with institutional genomic data to define the landscape of FGFR2/3-altered urothelial carcinoma. To identify mechanisms of erdafitinib resistance, a subset of patients underwent prospective cell-free (cf) DNA assessment.

Results:

FGFR3 alterations predictive of erdafitinib sensitivity were identified in 39% (199/504) of patients with non-muscle invasive, 14% (75/526) with muscle-invasive, 43% (81/187) with localized upper tract, and 26% (59/228) with metastatic specimens. One patient had a potentially sensitizing FGFR2 fusion. Among 27 FGFR3-altered cases with a primary tumor and metachronous metastasis, 7 paired specimens (26%) displayed discordant FGFR3 status. Erdafitinib achieved a response rate of 40% but median progression-free and overall survival of only 2.8 and 6.6 months, respectively (n = 32). Dose reductions (38%, 12/32) and interruptions (50%, 16/32) were common. Putative resistance mutations detected in cfDNA involved TP53 (n = 5), AKT1 (n = 1), and second-site FGFR3 mutations (n = 2).

Conclusions:

FGFR3 mutations are common in urothelial carcinoma, whereas FGFR2 alterations are rare. Discordance of FGFR3 mutational status between primary and metastatic tumors occurs frequently and raises concern over sequencing archival primary tumors to guide patient selection for erdafitinib therapy. Erdafitinib responses were typically brief and dosing was limited by toxicity. FGFR3, AKT1, and TP53 mutations detected in cfDNA represent putative mechanisms of acquired erdafitinib resistance.
Experience and Learning from the COVID-19 Pandemic in Portugal: Perceptions of Community Pharmacy Professionals
Authors: Advinha Ana Margarida , Santos Margarida C , Duarte-Ramos Filipa , Perdigão Margarida , Santos Patricia , Oliveira-Martins Sofia
Published: September 2023

Background: During the COVID-19 pandemic, community pharmacy (CP) professionals were among those who experienced the greatest risk of contracting SARS-CoV-2, which forced major adaptations. Objectives: The objectives of the study were to describe the changes implemented in CP professionals during the pandemic, understand the perception of professionals about their experience, and explore changes to remain. Methods: An observational and cross-sectional study was conducted via an online questionnaire (June–September 2020). The target population was CP professionals working in Portugal for >2 years and serving the public during the pandemic. Results: Of a total of 353 participants, 84% were female (mean age of 37.6 years), and 81% were pharmacists (mean professional experience of 12.9 years). In the management and organizational dimensions, the most mentioned changes were adaptation to legislative changes (90%), fluctuations in the treasury (82%), and reduction of working hours (46%). Only 2% resorted to simplified layoff. In the back office, there was a need to adapt stock management (93%) and purchase personal protective equipment (99%). In the front office, there was a change in service policies – wicket or conditional opening (92%), routes of the arrival of user requests (91%), and home delivery (82%). Physical changes occurred in 100% of pharmacies. The most frequently implemented procedures were the use of protection systems and PPE, articulation with hospital pharmacies for dispensing in proximity (75%), and training in this area (55%). Regarding interpersonal climate, improvements in the connection between team members are evident: increase in mutual help (57%), solidarity (54%), and group cohesion (50%); in the relationship with clients, the majority indicated the replacement of the usual user by third parties (71%), and changes in communication channels (increase in use of technological means 68%). Conclusions: Results illustrate the profound impact of the pandemic on CP professionals, both professionally and personally. It also highlights the importance of their roles in proximity and community support.
Unanticipated Enhancement of Intestinal TG Output by Apoc3 ASO Inhibition
Authors: Syed-Abdul Majid Mufaqam , Tian Lili , Lewis Gary F.
Published: September 2023

BACKGROUND:

The objective of this study was to investigate whether apoC3 (apolipoprotein C3) inhibition with an antisense oligonucleotide (ASO) modulates intestinal triglyceride secretion.

METHODS:

Sprague-Dawley rats were treated with subcutaneous injections of apoC3 ASO 25 mg/kg twice weekly or inactive ASO for 4 weeks before the assessment of lymph flow, triglyceride and apoB48 (apolipoprotein B48) appearance in the lymph. Rats were surgically implanted with catheters in the mesenteric lymph duct and duodenum. Following an overnight fast, an intraduodenal lipid bolus (1.5-mL intralipid) was administered. Lymph fluid was collected for the following 4 hours to compare effects on lymph flow, lymph triglyceride and apoB48 concentration, and secretion. To assess suppression of apoC3 expression and protein abundance by apoC3 ASO compared with inactive ASO (placebo), intestinal and hepatic tissues were collected from a subset of animals before (fasting) and after an enteral lipid bolus (post-lipid).

RESULTS:

ApoC3 ASO significantly reduced apoC3 mRNA expression in the liver compared with inactive ASO (fasting: 42%,
P
=0.0048; post-lipid: 66%,
P
<0.001) and in the duodenum (fasting: 29%,
P
=0.0424; post-lipid: 53%,
P
=0.0120). As expected, plasma triglyceride also decreased significantly (fasting: 74%,
P
<0.001; post-lipid: 33%,
P
=0.0276). Lymph flow and cumulative lymph volume remained unchanged following apoC3 ASO therapy; however, lymph triglyceride, but not apoB48 output, increased by 38% (ANOVA,
P
<0.001). Last, no changes were observed in stool triglyceride, intestinal fat (quantified via oil red O staining), and expression of mRNAs involved in triglyceride synthesis, lipid droplet formation, and chylomicron transport and secretion.

CONCLUSIONS:

Despite the marked reduction in plasma triglyceride concentration that occurs with apoC3 ASO inhibition, intestinal triglyceride output surprisingly increased rather than decreased. These data demonstrate that the reduction of intestinal triglyceride output does not contribute to the potent plasma triglyceride-lowering observed with this novel therapy for hypertriglyceridemia. Further studies are required to explore the mechanism of this intestinal effect.
PAR4 Inhibition Reduces Coronary Artery Atherosclerosis and Myocardial Fibrosis in SR-B1/LDLR Double Knockout Mice
Authors: Lee Samuel K. , Malik Rida A. , Zhou Ji , Wang Wei , Gross Peter L. , Weitz Jeffrey I. , Ramachandran Rithwik , Trigatti Bernardo L.
Published: September 2023

BACKGROUND:

SR-B1 (scavenger receptor class B type 1)/LDLR (low-density lipoprotein receptor) double knockout mice fed a high-fat, high-cholesterol diet containing cholate exhibit coronary artery disease characterized by occlusive coronary artery atherosclerosis, platelet accumulation in coronary arteries, and myocardial fibrosis. Platelets are involved in atherosclerosis development, and PAR (protease-activated receptor) 4 has a prominent role in platelet function in mice. However, the role of PAR4 on coronary artery disease in mice has not been tested.

METHODS:

We tested the effects of a PAR4 inhibitory pepducin (RAG8) on diet-induced aortic sinus and coronary artery atherosclerosis, platelet accumulation in atherosclerotic coronary arteries, and myocardial fibrosis in SR-B1/LDLR double knockout mice. SR-B1/LDLR double knockout mice were fed a high-fat, high-cholesterol diet containing cholate and injected daily with 20 mg/kg of either the RAG8 pepducin or a control reverse-sequence pepducin (SRQ8) for 20 days.

RESULTS:

Platelets from the RAG8-treated mice exhibited reduced thrombin and PAR4 agonist peptide–mediated activation compared with those from control SRQ8-treated mice when tested ex vivo. Although aortic sinus atherosclerosis levels did not differ, RAG8-treated mice exhibited reduced coronary artery atherosclerosis, reduced platelet accumulation in atherosclerotic coronary arteries, and reduced myocardial fibrosis. These protective effects were not accompanied by changes in circulating lipids, inflammatory cytokines, or immune cells. However, RAG8-treated mice exhibited reduced VCAM-1 (vascular cell adhesion molecule 1) protein levels in nonatherosclerotic coronary artery cross sections and reduced leukocyte accumulation in atherosclerotic coronary artery cross sections compared with those from SRQ8-treated mice.

CONCLUSIONS:

The PAR4 inhibitory RAG8 pepducin reduced coronary artery atherosclerosis and myocardial fibrosis in SR-B1/LDLR double knockout mice fed a high-fat, high-cholesterol diet containing cholate. Furthermore, RAG8 reduced VCAM-1 in nonatherosclerotic coronary arteries and reduced leukocyte and platelet accumulation in atherosclerotic coronary arteries. These findings identify PAR4 as an attractive target in reducing coronary artery disease development, and the use of RAG8 may potentially be beneficial in cardiovascular disease.
Changes in Cardiovascular Spending, Care Utilization, and Clinical Outcomes Associated With Participation in Bundled Payments for Care Improvement – Advanced
Authors: Shashikumar Sukruth A. , Zheng Jie , Orav E. John , Epstein Arnold M. , Joynt Maddox Karen E.
Published: September 2023

BACKGROUND:

Bundled Payments for Care Improvement – Advanced (BPCI-A) is a Medicare initiative that aims to incentivize reductions in spending for episodes of care that start with a hospitalization and end 90 days after discharge. Cardiovascular disease, an important driver of Medicare spending, is one of the areas of focus BPCI-A. It is unknown whether BPCI-A is associated with spending reductions or quality improvements for the 3 cardiovascular medical events or 5 cardiovascular procedures in the model.

METHODS:

In this retrospective cohort study, we conducted difference-in-differences analyses using Medicare claims for patients discharged between January 1, 2017, and September 30, 2019, to assess differences between BPCI-A hospitals and matched nonparticipating control hospitals. Our primary outcomes were the differential changes in spending, before versus after implementation of BPCI-A, for cardiac medical and procedural conditions at BPCI-A hospitals compared with controls. Secondary outcomes included changes in patient complexity, care utilization, healthy days at home, readmissions, and mortality.

RESULTS:

Baseline spending for cardiac medical episodes at BPCI-A hospitals was $25 606. The differential change in spending for cardiac medical episodes at BPCI-A versus control hospitals was $16 (95% CI, −$228 to $261;
P
=0.90). Baseline spending for cardiac procedural episodes at BPCI-A hospitals was $37 961. The differential change in spending for cardiac procedural episodes was $171 (95% CI, −$429 to $772;
P
=0.58). There were minimal differential changes in physicians’ care patterns such as the complexity of treated patients or in their care utilization. At BPCI-A versus control hospitals, there were no significant differential changes in rates of 90-day readmissions (differential change, 0.27% [95% CI, −0.25% to 0.80%] for medical episodes; differential change, 0.31% [95% CI, −0.98% to 1.60%] for procedural episodes) or mortality (differential change, −0.14% [95% CI, −0.50% to 0.23%] for medical episodes; differential change, −0.36% [95% CI, −1.25% to 0.54%] for procedural episodes).

CONCLUSIONS:

Participation in BPCI-A was not associated with spending reductions, changes in care utilization, or quality improvements for the cardiovascular medical events or procedures offered in the model.
Advanced Progress of the Relationship Between Antihypertensive Drugs and Bone Metabolism
Authors: Zhang Ruixing , Yin Hongtao , Yang Mengdi , Lei Xianqiong , Zhen Donghu , Zhang Zheng
Published: September 2023

Hypertension and osteoporosis are common comorbidities among elderly individuals. Drug therapy has been widely used in clinical practice as the preferred antihypertensive treatment. Therefore, antihypertensive drugs have become some of the most commonly prescribed drugs in healthcare settings. However, antihypertensive drugs have different effects on bone metabolism. The results of animal and clinical studies on the effects of antihypertensive drugs on osteoporosis or fracture risk are controversial and have aroused widespread concern among clinicians. Recent studies found that angiotensin receptor blockers, selective β-adrenergic receptor blockers, and thiazide diuretics might improve bone trabecular number and bone mineral density by stimulating osteoblast differentiation, reducing osteoclast generation, and other mechanism. Furthermore, nonselective β-adrenergic receptor blockers and dihydropyridine calcium channel blockers were found to have no significant relationship with bone mineral density or bone strength, and α-adrenergic receptor blockers and loop diuretics might increase fracture risk by decreasing bone mineral density. This article aimed to review previous animal experiments, clinical studies, and meta-analyses focusing on the effects of different antihypertensive drugs on bone metabolism, and to provide a new approach for the prevention and treatment of osteoporosis.
The Domain of Formal Matching in Sluicing
Authors: Anand Pranav , Hardt Daniel , McCloskey James
Published: September 2023

This article is concerned with the role of syntax in the licensing of sluicing in English. It amends and provides new support for a proposal made by Rudin (2019) in which syntax plays a crucial but circumscribed role: crucial in that antecedents are required; circumscribed in that matching with an antecedent holds only with respect to a proper subpart of the elided clause—its argumental core.
Pierre Janet’s Secret Garden, or the Botanical Collection of a Psychopathologist
Authors: Serina Florent
Published: September 2023

Pierre Janet, the French philosopher, psychotherapist, and doctor (1859–1947), has often been presented as one of the central figures in contemporary clinical psychology, whose practices and ideas are said to have anticipated those of Sigmund Freud, before becoming a fierce critic of psychoanalysis. What is less well known, however, is that he was also an experienced botanist. The recent discovery of his personal herbarium, which was long thought to be lost, leads historians to address a curious paradox. Unlike his professional papers, of which only a fraction remains, his entire collection built up over 70 years of passionate collecting has been preserved. Thus although the world-famous clinician, bound to medical secrecy, still resists historical exposition, the hitherto unknown amateur naturalist appears in the full light of day. Even though Janet was careful not to hastily amalgamate the study of human behaviour to that of plants, detailed examination of his abundant written work shows that these two disciplines could overlap on occasions.
Producing Authenticity, Difference and Extremism
Authors: van den Brandt Nella , van den Berg Mariecke , Meijer Béracha
Published: September 2023

In this article, we explore the framing of religious converts by Dutch and Flemish newspapers in the period 1991–2017. We focus on the differences and commonalities in ways of talking about religious conversions to Christianity and Islam. Our approach is to probe the ‘figure’ of the convert: How is the religious convert framed and understood? We present a typology of figures of the religious convert emerging from our material, including the ‘authentic seeker’, the ‘exemplary believer’, the ‘cultural other’, the ‘victim’, the ‘opportunist’ and the ‘extremist’. This approach allows us to explore how newspapers promote particular notions of conversion, and to show that the framing of religious converts is mediated by religion, gender, race and citizenship.
“Assalamu ʿAlaykum, Can We Add This Sister?”
Authors: ter Laan Nina
Published: September 2023

This article examines the use of a WhatsApp chat group by Dutch and Belgian Muslim women (born or converted), who are considering or made hijra (religiously inspired migration to a Muslim country) to Morocco. I argue that WhatsApp plays a crucial role in facilitating and narrating these women’s migration by providing a support network and shaping a gendered sense of community and religious belonging. Drawing on theories of religion and gender, migration, and digital media, I conceptualize WhatsApp in the context of hijra to Morocco as a social practice of homemaking that helps alleviate the precarious conditions these women find themselves in. This article also illustrates the complex entanglement of offline and online realities by highlighting how my interlocutors’ interactions in this WhatsApp group foster a trans-local Muslim ‘sisterhood,’ that informs their offline practices and experiences of hijra to Morocco.
Between Symbolic Distancing and Following Desires
Authors: Rau Vanessa
Published: September 2023

Over the past decades, Judaism and Jewishness have been subject to transformation and more fluid boundaries. This article looks at women’s conversions to Judaism in Germany. Analyzing differing biographical trajectories, the article shows how individuals negotiate their desire to become Jewish, which is often closely related to an experience in Israel and a Jewish partner. Arguing that the context makes the conversion, I show how desires and negotiations are deeply entangled with the socio-historical context of German society as well as with the erotic and sexuality. I demonstrate how becoming Jewish presents a way of symbolically distancing oneself from biographical experiences of difference, which are negotiated in and through the conversion. As these conversions are not uncontested, I also show how becoming part of Jewish socialities evokes a negotiation of one’s positionality at the intersection of gender and religion.
Looks can be deceiving: recently published Bacopa llanorum (Plantaginaceae) is synonymous with Lindernia brachyphylla (Linderniaceae) and B. debilis is an unnecessary combination
Authors: SCATIGNA ANDRÉ VITO
Published: September 2023

Important efforts toward exploring the flora of the Orinoquia region of Colombia and Venezuela resulted in several novelties, including the recently described Bacopa llanorum. Here I present a reinterpretation of the identity of this species and place it under the synonymy of Lindernia brachyphylla. Additionally, I make a remark on the status of the combination Bacopa debilis and propose a second step lectotypification for Herpestis reptans. The content of this contribution highlights the importance of specimen exchange between megadiverse countries and the crucial role of taxon experts in peer review of papers describing new species.
The Macro- and Microphysical Response Characteristics of the Multicell Hailstorm Hail-Suppression Operation: Case Study
Authors: Lu Yuan , Zhou Yunjun , Zou Shuping , Yang Zhe , Zeng Yong
Published: September 2023

This study analyzed the macro- and microphysical response characteristics of a typical multicell hailstorm after seeding on 27 April 2019 in Weining, China, using X-band dual-polarization radar (YLD1-D) data. An improved X-pol hydrometeor identification algorithm was employed for hydrometeor identification. According to the diffusion of the seeding agents, the seeded hailstorm was graded into three study regions, and the evolution of the seeded hailstorm was divided into four periods. The response characteristics of the seeded hailstorm in each region and period were compared and analyzed. The results show that 1) macroscopically, the decrease in the reflectivity and the height of strong echo mainly occurred in the seeded period, whereas the decrease in the echo top and the height of the storm was mainly in the postseeded period; the echo height variation of the unseeded hailstorm is obviously different from that of the seeded hailstorm; and 2) from the microscopic perspective, the decrease in low-density graupel and supercooled water and the increase in ice crystals and aggregates in the seeded region mainly occurred in the seeded period, which was consistent with the time required for the “benefit competition” after the silver iodide completed nucleation. When compared with the seeded region, the hydrometeors in the unseeded region had an opposite trend (or an in-phase trend with an obviously lower changing rate), which further indicated the impact of the artificial ice nuclei on microphysical processes in the seeded region. For hailstorms with a high content of supercooled droplets and graupel, the key mechanisms of hail suppression are “cloud water glaciation,” “beneficial competition,” and “early rainout.”
Synoptic and Mesoscale Aspects of Exceptional Fire Weather during the New Year Period 2019–20 in Southeastern New South Wales, Australia
Authors: Fox-Hughes Paul
Published: September 2023

Extreme fire weather and fire behavior occurred during the New Year’s Eve period 30–31 December 2019 in southeast New South Wales, Australia. Fire progressed rapidly during the late evening and early morning periods, and significant extreme pyrocumulonimbus behavior developed, sometimes repeatedly in the same area. This occurred within a broader context of an unprecedented fire season in eastern Australia. Several aspects of the synoptic and mesoscale meteorology are examined, to identify contributions to fire behavior during this period. The passage of a cold front through the region was a key factor in the event, but other processes contributed to the severity of fire weather. Additional important features during this period included the movement of a negatively tilted upper-tropospheric trough, the interaction of the front with topography, and the occurrence of low-level overnight jets and of horizontal boundary layer rolls in the vicinity of the fireground.

Significance Statement

Wildfires and the weather that promotes their ignition and spread are a threat to communities and natural values globally, even in fire-adapted landscapes such as the western United States and Australia. In particular, savanna in the north of Australia regularly burns during the dry season while forest and grassland in the south burn episodically, mostly during the summer. Here, we examine the weather associated with destructive fires that occurred in southeast New South Wales, Australia, in late 2019. Weather and climate factors at several scales interacted to contribute to fire activity that was unusually dangerous. For meteorologists and emergency managers, case studies such as this are valuable to highlight conditions that may lead to future similar events. This case study also identified areas where improvements in fire weather service can be made, including the incorporation of more detailed weather information into models of fire behavior.
Mental health and current issues of migrant workers in Japan: A cross-sectional study of Vietnamese workers
Authors: Uezato Akihito , Sakamoto Kohei , Miura Mieko , Futami Akane , Nakajima Toshihiko , Quy Pham Nguyen , Jeong Soi , Tomita Shigeru , Saito Yoshihisa , Fukuda Yui , Yoshizawa Nonoka , Taguchi Atsuko
Published: September 2023

Background:

Over the past 5 years, the number of Vietnamese migrant workers in Japan has grown rapidly to become the largest group of migrant workers in the country. They hold various statuses of residence and are subjected to multifactorial stressors.

Aims:

The current study’s aim is to investigate the association between psychological distress experienced by Vietnamese workers and their work environment. Another aim is to discuss issues involving migrant workers by comparing the characteristics of workers in the major statuses of residence.

Methods:

The study applied a cross-sectional design, and included a nationwide self-administered online questionnaire that was conducted in Vietnamese in 2022. The questionnaire included the Kessler Psychological Distress Scale (K10), workplace interpersonal factors as well as factors related to work and health. A multiple logistic regression analysis was conducted to investigate factors associated with psychological distress.

Results:

Of 933 Vietnamese workers, 37% were grouped as distressed under the K10 cutoff. Fewer opportunities to speak with Japanese co-workers, lower welfare and workload ratings, and the visa statuses including ‘Technical Intern Training’ were significantly associated with psychological distress. Unexpectedly, those in ‘Engineer/Specialist in Humanities/International Services (ESI)’ category who are deemed to hold better conditions demonstrated the highest amounts of distress.

Conclusion:

Outside of unsatisfactory working environments, differing situations depending on status of residence could produce various sources of distress. The difficult aspects of Japan’s distinct culture seem to contribute to their distress, especially for those who have more interactions with Japanese co-workers. A push for a multicultural society, where migrant workers can pursue proactive life designs of their own choosing, is warranted.
Favorable Patient-Reported, Clinical, and Functional Outcomes 2 Years After ACL Repair and InternalBrace Augmentation Compared With ACL Reconstruction and Healthy Controls
Authors: Müller Sebastian , Bühl Linda , Nüesch Corina , Pagenstert Geert , Mündermann Annegret , Egloff Christian
Published: September 2023

Background:

Recently, interest in anterior cruciate ligament (ACL) preservation and repair after proximal ACL tears has been resurrected. Although good clinical outcomes have been reported in the literature with adequate patient selection, to date detailed scientific evidence for the functional benefit of primary ACL repair with ligament augmentation is scarce.

Purpose:

To compare patient-reported, clinical, and functional outcomes in patients 2 years after ACL repair and InternalBrace augmentation (ACL-IB) with age- and sex-matched patients 2 years after ACL reconstruction (ACL-R) and with matched healthy controls.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

In total, 29 patients 2 years after ACL-IB, 27 sex- and age- matched patients 2 years after ACL-R (hamstring autografts), and 29 matched healthy controls were included. Patient-reported outcomes were assessed using the International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, EQ-5D-5L, Tegner Activity Scale, and Anterior Cruciate Ligament Return to Sports after Injury scale. Surgery time was recorded. For clinical outcomes, range of motion and thigh and shank circumference were measured, and passive anterior translation was determined using the Rolimeter. Isokinetic muscle strength was measured using a Biodex dynamometer. The limb symmetry index (operated/contralateral or nondominant/dominant × 100), side-to-side differences (operated – contralateral, nondominant – dominant), and hamstring-quadriceps ratios were calculated for functional parameters. Failure and reoperation rates were not compared.

Results:

Two years after surgery, patients treated with ACL-IB showed good to excellent patient-reported outcomes comparable with those of patients after ACL-R. Surgery time, including concomitant surgeries, was significantly shorter in the ACL-IB group (mean, 81 minutes) compared with the ACL-R group (mean, 97 minutes) ( P = .024). Isokinetic muscle strength was comparable between patient groups without significant differences in extensor and flexor strength or in hamstring-quadriceps ratios.

Conclusion:

These results suggest that ACL-IB achieves comparable patient-reported, clinical, and functional outcomes with ACL-R at 2 years postoperatively and, after careful patient selection, should be considered as a valuable early treatment alternative for proximal ACL tears.

Registration:

NCT04429165 (ClinicalTrials.gov identifier).
Toward Urban-Oriented Shopping Center Development in the Post-COVID Era? Learning from Shopping Centers with Apple Store
Authors: Rao Fujie , Liu Luofu
Published: September 2023

The persistence of post-COVID shopping centers arguably depends on the urban experience. However, contemporary shopping morphologies and their preparedness for urban transitions are not well understood. We tackled the research gap through a mixed-methods approach combining spatial and quantitative analysis, using a large number of shopping centers with Apple Store in the United States. Our key findings feature three “E” (experiment, experience, and emergence) s. Contemporary shopping morphologies embody various typological experiments while being geared toward the urban experience. The emergence of the urban experience in shopping centers could be stimulated in urban neighborhoods or the novel fusion between the street and town square experience.
Safety and efficacy of zanubrutinib in relapsed/refractory marginal zone lymphoma: final analysis of the MAGNOLIA study
Authors: Opat Stephen , Tedeschi Alessandra , Hu Bei , Linton Kim M. , McKay Pamela , Leitch Sophie , Coleman Morton , Zinzani Pier Luigi , Jin Jie , Sun Mingyuan , Sobieraj-Teague Magdalena , Browett Peter , Ke Xiaoyan , Thieblemont Catherine , Ardeshna Kirit , Bijou Fontanet , Walker Patricia , Hawkes Eliza A. , Ho Shir-Jing , Zhou Keshu , Liang Zhiyu , Xu Jianfeng , Tankersley Chris , Delarue Richard , Co Melannie , Trotman Judith
Published: September 2023

The primary analysis of MAGNOLIA, an open-label, single-arm, multicenter, phase 2 study, demonstrated that the next-generation Bruton tyrosine kinase (BTK) inhibitor zanubrutinib provided a high overall response rate (ORR) in patients with relapsed/refractory marginal zone lymphoma (R/R MZL), with a favorable safety/tolerability profile. Presented here, is the final analysis of MAGNOLIA, performed to characterize the durability of response and longer-term safety and tolerability. Zanubrutinib (160 mg twice daily) was evaluated in 68 patients with R/R MZL who had received at least 1 anti-CD20–directed regimen. The primary end point was independent review committee (IRC)-assessed ORR. Secondary end points included investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), health-related quality of life, safety, and tolerability. With a median follow-up of 27.4 months, the IRC-assessed ORR was 68.2% (95% confidence interval [CI], 55.6-79.1), with a 24-month DOR event-free rate of 72.9% (95% CI, 54.4-84.9). PFS and OS at 24 months were 70.9% (95% CI, 57.2-81.0) and 85.9% (95% CI, 74.7-92.4), respectively. The zanubrutinib safety profile was consistent with the primary analysis, with no new safety signals observed. Atrial fibrillation/flutter (n = 2 [2.9%]) and hypertension (n = 3 [4.4%]) were uncommon. Neutropenia (n = 8 [11.8%]) was the most common grade ≥3 adverse event. In this final analysis of MAGNOLIA, zanubrutinib demonstrated sustained clinical responses beyond 2 years, with 73% of responders alive and progression free. Zanubrutinib continued to demonstrate a favorable safety/tolerability profile with the additional time on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03846427.
SBP1 promotes tumorigenesis of thyroid cancer through TXN/NIS pathway
Authors: Ma Jiancang , Huang Xin , Xu Jinkai , Li Zongyu , Lai Jingyue , Shen Yawei , Zhao Jun , Sun Xuejun , Ma Lieting
Published: September 2023

Background

As the tissue with the highest selenium content in the body, the occurrence and development of thyroid cancer are closely related to selenium and selenoproteins. Selenium-binding protein 1 (SBP1) has been repeatedly implicated in several cancers, but its role and molecular mechanisms in thyroid cancer remains largely undefined.

Methods

The expression of SBP1, sodium/iodide symporter (NIS) and thioredoxin (TXN) were analyzed in clinical samples and cell lines. Cell counting kit-8 (CCK-8) and tube formation assays were used to analyze the cell viability and tube formation of cells. Immunofluorescence was used to determine the expression of the NIS. Co-immunoprecipitation (Co-IP) assay was carried out to verify the interaction of SBP1 with TXN. The mouse xenograft experiment was performed to investigate the growth of thyroid cancer cells with SBP1 knockdown in vivo.

Results

SBP1 was significantly increased in human thyroid cancer tissues and cells, especially in anaplastic thyroid cancer. Overexpression of SBP1 promoted FTC-133 cell proliferation, and the culture supernatant of SBP1-overexpression FTC-133 cells promoted tube formation of human retinal microvascular endothelial cells. Knockdown of SBP1, however, inhibited cell proliferation and tube formation. Furthermore, overexpression of SBP1 inhibited cellular differentiation of differentiated thyroid cancer cell line FTC-133, as indicated by decreased expression of thyroid stimulating hormone receptors, thyroglobulin and NIS. Knockdown of SBP1, however, promoted differentiation of BHT101 cells, an anaplastic thyroid cancer cell line. Notably, TXN, a negative regulator of NIS, was found to be significantly upregulated in human thyroid cancer tissues, and it was positively regulated by SBP1. Co-IP assay implied a direct interaction of SBP1 with TXN. Additionally, TXN overexpression reversed the effect of SBP1 knockdown on BHT101 cell viability, tube formation and cell differentiation. An in vivo study found that knockdown of SBP1 promoted the expression of thyroid stimulating hormone receptors, thyroglobulin and NIS, as well as inhibited the growth and progression of thyroid cancer tumors.

Conclusion

SBP1 promoted tumorigenesis and dedifferentiation of thyroid cancer through positively regulating TXN.
Bending responses of self-shaping wood bilayers: comparison between adsorption and desorption processes
Authors: Peng Hui , Liu Zhiting , Zhu Jianyi , Jiang Jiali , Lyu Jianxiong , Zhan Tianyi
Published: September 2023

Inspired by biological materials, the self-shaping wood composites induced by relative humidity (RH) have been investigated over the last decade. In this study, a wood bilayer was fabricated by assembling two layers with perpendicular fiber orientation in a series of thickness ratios and initial moisture contents (iMC). The self-shaping response of the wood bilayer was explored as a function of its configuration, and the discrepancies between moisture adsorption and desorption processes were clarified. Higher iMC limited the evolution of curvature. During both the adsorption and desorption processes, a reversed bending response was observed, and there was a hysteretic bending behavior between them. Repeatable bending was achieved during the cyclic ad/desorption process, and a larger hysteresis loop was observed at a lower thickness ratio. Finite-element analysis showed that the maximum stress occurred at the interface between the active and passive layers, and larger thickness ratios had lower maximum stress. In addition, the bilayer composed of a 200 μm passive layer and a 400 μm active layer with 0.6% iMC was found to be the most sensitive to RH change. The results of this study elucidate the moisture-dependent bending response of wood bilayers and provide the possibility of precisely controlling the curvature of self-shaping wood composites in industrial applications.
Rural family physician use of point-of-care ultrasonography: experiences of primary care providers in British Columbia, Canada
Authors: Kornelsen Jude , Ho Hilary , Robinson Virginia , Frenkel Oron
Published: September 2023

Background

In British Columbia (BC), rural and remote areas lack proximal access to radiographic services. Poor access to radiographic services in rural settings presents a challenge to timely diagnosis and screening across many disease states and healthy pregnancies. As a solution to the lack of access to radiographic services in rural settings, the Rural Coordination Centre of BC (RCCbc) supported rural Family Physicians (FPs) wishing to use PoCUS through the Intelligent Network for PoCUS (IN PoCUS) program. This study evaluates FPs’ experience and use of PoCUS in their clinical practice.

Methods

This qualitative study conducted in-depth virtual interviews with 21 FPs across rural BC. The interview asked participants’ motivation to participate in the RCCbc program, the type of training they received, their current use of PoCUS, their experience with the technology, and their experience interacting with specialists in regional centres. Thematic analysis of findings was undertaken.

Results

This study used Rogers’ framework on the five elements of diffusion of innovation to understand the factors that impede and enable the adoption of PoCUS in rural practice. Rural FPs in this study differentiated PoCUS from formal imaging done by specialists. The adoption of PoCUS was viewed as an extension of physical exams and was compatible with their values of providing generalist care. This study found that the use of PoCUS provided additional information that led to better clinical decision-making for triage and allowed FPs to determine the urgency for patient referral and transport to tertiary hospitals. FPs also reported an increase in job satisfaction with PoCUS use. Some barriers to using PoCUS included the time needed to be acquainted with the technology and learning how to integrate it into their clinical flow in a seamless manner.

Conclusion

This study has demonstrated the importance of PoCUS in improving patient care and facilitating timely diagnosis and treatment. As the use of PoCUS among FPs is relatively new in Canada, larger infrastructure support such as improving billing structures, long-term subsidies, educational opportunities, and a quality improvement framework is needed to support the use of PoCUS among rural FPs.
Family relationships as a source of narrative identity of people with advanced dementia
Authors: Kłosińska Urszula , Leszko Magdalena
Published: September 2023

Background

The growing body of research on narrative identity, while helpful, rarely focuses on people with dementia. In this paper, we explore how individuals living with advanced dementia construct their narrative identities in relation to their family experiences, which play a crucial role in shaping identity as shown by recent studies.

Methods

We conducted a qualitative study using data from 15 semi-structured interviews with people aged 66 to 94 who have advanced dementia. The data were analyzed using a textual-oriented discourse analysis.

Results

We identified two discourses—autobiographical and economic—that organize their narrative identities. Through the autobiographical discourse, participants emphasized their sense of belonging within a social group and their role as custodians of family identity. Within the economic discourse, they negotiated their social utility and value, particularly in response to demeaning discourses targeting individuals who do not accumulate wealth. In the structural analysis, we identified two narrative types—looped or unfolding—that depend on their affective experiences related to their family. We especially explored how the repetition of narrative threads by individuals with dementia might indicate a traumatic background rather than just memory disruptions.

Conclusions

This study provides insights into the narrative identities of individuals with advanced dementia, shedding light on the intersection of family experiences and identity formation in this population.
Unraveling virulence determinants in extended-spectrum beta-lactamase-producing Escherichia coli from East Africa using whole-genome sequencing
Authors: Sserwadda Ivan , Kidenya Benson R. , Kanyerezi Stephen , Akaro Inyasi Lawrence , Mkinze Baraka , Mshana Stephen E. , Hashim Suhaila O. , Isoe Everlyne , Seni Jeremiah , Joloba Moses L. , Mboowa Gerald
Published: September 2023

Escherichia coli significantly causes nosocomial infections and rampant spread of antimicrobial resistance (AMR). There is limited data on genomic characterization of extended-spectrum β-lactamase (ESBL)-producing E. coli from African clinical settings. This hospital-based longitudinal study unraveled the genetic resistance elements in ESBL E. coli isolates from Uganda and Tanzania using whole-genome sequencing (WGS). A total of 142 ESBL multi-drug resistant E. coli bacterial isolates from both Tanzania and Uganda were sequenced and out of these, 36/57 (63.1%) and 67/85 (78.8%) originated from Uganda and Tanzania respectively. Mutations in RarD, yaaA and ybgl conferring resistances to chloramphenicol, peroxidase and quinolones were observed from Ugandan and Tanzanian isolates. We reported very high frequencies for blaCTX−M−15 with 11/18(61.1%), and blaCTX−M−27 with 12/23 (52.1%), blaTEM−1B with 13/23 (56.5%) of isolates originating from Uganda and Tanzania respectively all conferring resistance to Beta-lactam-penicillin inhibitors. We observed chloramphenicol resistance-conferring gene mdfA in 21/23 (91.3%) of Tanzanian isolates. Extraintestinal E. coli sequence type (ST) 131 accounted for 5/59 (8.4%) of Tanzanian isolates while enterotoxigenic E. coli ST656 was reported in 9/34 (26.4%) of Ugandan isolates. Virulence factors originating from Shigella dysenteriae Sd197 (gspC, gspD, gspE, gspF, gspG, gspF, gspH, gspI), Yersinia pestis CO92 (irp1, ybtU, ybtX, iucA), Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 (csgF and csgG), and Pseudomonas aeruginosa PAO1 (flhA, fliG, fliM) were identified in these isolates. Overall, this study highlights a concerning prevalence and diversity of AMR-conferring elements shaping the genomic structure of multi-drug resistant E. coli in clinical settings in East Africa. It underscores the urgent need to strengthen infection-prevention controls and advocate for the routine use of WGS in national AMR surveillance and monitoring programs.

Availability of WGS analysis pipeline: the rMAP source codes, installation, and implementation manual can free be accessed via https://github.com/GunzIvan28/rMAP.
Applicability of the low-grade inflammation score in predicting 90-day functional outcomes after acute ischemic stroke
Authors: Zhou Yang , Luo Yufan , Liang Huazheng , Zhong Ping , Wu Danhong
Published: September 2023

Background and purpose

The low-grade inflammation (LGI) score, a novel indicator of chronic LGI, combines C-reactive protein (CRP), leukocyte counts, the neutrophil/lymphocyte ratio (NLR), and the platelet (PLT) count to predict outcomes of patients with various conditions, such as cardiovascular diseases, cancers, and neurodegenerative diseases. However, few studies have examined the role of the LGI score in predicting functional outcomes of patients with ischemic stroke. The present study aimed to evaluate the association between the LGI score and functional outcomes of patients with ischemic stroke.

Methods

A total of 1,215 patients were screened in the present study, and 876 patients were finally included in this retrospective observational study based on the inclusion and exclusion criteria. Blood tests were conducted within 24 h of admission. Severity of ischemic stroke was assessed using the NIHSS score with severe stroke denoted by NIHSS > 5. Early neurological deterioration (END) was defined as an increment in the total NIHSS score of ≥ 2 points within 7 days after admission. Patient outcomes were assessed on day 90 after stroke onset using the modified Rankin Scale (mRS).

Results

The LGI score was positively correlated with baseline and the day 7 NIHSS scores (R2 = 0.119, p < 0.001;R2 = 0.123, p < 0.001). Multivariate regression analysis showed that the LGI score was an independent predictor of stroke severity and END. In the crude model, the LGI score in the fourth quartile was associated with a higher risk of poor outcomes on day 90 compared with the LGI score in the first quartile (OR = 5.02, 95% CI: 3.09–8.14, p for trend < 0.001). After adjusting for potential confounders, the LGI score in the fourth quartile was independently associated with poor outcomes on day 90 (OR = 2.65, 95% CI: 1.47–4.76, p for trend = 0.001). Finally, the ROC curve analysis showed an AUC of 0.682 for poor outcomes on day 90 after stroke onset.

Conclusion

The LGI score is strongly correlated with the severity of acute ischemic stroke and that the LGI score might be a good predictor for poor outcomes on day 90 in patients with acute ischemic stroke.
Mental health related stigma in Romania: systematic review and narrative synthesis
Authors: Manescu Elena A. , Henderson Claire , Paroiu Ciprian R. , Mihai Adriana
Published: September 2023

Background

Stigma related to mental illness is increasingly and more effectively addressed. Although more research is being conducted, there is relatively little from low and middle-income countries, with former Soviet bloc countries identified as a particular contributor to this evidence gap. Romania struggles with mental health stigma at many levels. The aim of this review was to bring together all relevant data regarding stigma and discrimination related to mental illness as well as actions to address these problems in Romania in order to prioritise further stigma research and identify priority targets for stigma reduction.

Methods

A systematic literature search was conducted in three online databases and grey literature. After the analysis of full manuscripts, four were excluded based on lack of relevance or incomplete data reporting. Quality assessment was performed for included studies using the Mixed Methods Appraisal Tool (MMAT) and the narrative was synthesized based on the research questions.

Results

The review included fifteen studies, the majority having a cross-sectional design. Stigma related to mental illness in Romania, has an impact on help-seeking attitudes and behaviours, workplace environment and social relationships of people with mental health problems. Negative stereotypes are maintained and validated by mass media reports. Significant stigma in healthcare and mental care settings has also been observed. Self-stigma was less frequently reported than public stigma. Despite a few stigma reduction actions, no rigorous evaluation of content, delivery and effectiveness has been conducted and no empirical evidence has been published.

Conclusions

Based on this review, three lines of action are recommended in Romania. Increase research concerning stigma in healthcare and mental care settings and use behavioural outcomes. Develop and deliver evidence-based tailored interventions to reduce stigma in identified priority subgroups of the population and ensure rigorous evaluation and scientific dissemination. Elaborate guidelines for working with community stigma and advocate for structural changes.