bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding dentatorubral-pallidoluysian atrophy (DRPLA) symptoms and impacts on daily life: a qualitative interview study with patients and caregivers
Authors: Contesse Marielle G. , Woods Rebecca J. , Leffler Mindy , Prades Silvia , Greenfield Julie , Compton Andrea , Carroll Jeffrey B.
Published: May 2024

Background:

Dentatorubral–pallidoluysian atrophy (DRPLA) is a rare, neurodegenerative disorder with no disease-modifying treatments. There is a dearth of information in the literature about the patient and caregiver experience living with DRPLA.

Objectives:

This study aimed to (1) understand symptoms experienced by adult- and juvenile-onset DRPLA populations and their impact on daily life and (2) explore patient and caregiver treatment goals and clinical trial participation preferences.

Design:

The study was a qualitative interview study.

Methods:

Interviews were conducted remotely with adult patients with DRPLA and caregivers. Participants described patient symptoms and the impact of those symptoms on daily life, and they discussed treatment goals and potential clinical trial participation. There were 18 patients described in the interviews with two patients and seven caregivers. Some participants were caregivers to multiple patients with DRPLA.

Results:

Interview transcripts were coded for themes, and reported symptoms were summarized with descriptive statistics. Adult-onset patients ( N = 7) experienced difficulty with ataxia (100%), cognition (100%), fine motor skills (100%), gross motor skills (100%), speech (100%), personality changes (100%), and seizures (57%). Juvenile-onset patients ( N = 11) experienced difficulty with ataxia (100%), sleep (100%), speech (100%), jerking/twitching (83%), behavior (82%), cognition (82%), fine motor skills (82%), gross motor skills (82%), sensory sensitivity (75%), and seizures (64%). When considering aspects of DRPLA to target for future treatment, patients prioritized ataxia/mobility (100%), juvenile-onset caregivers prioritized ataxia/mobility (60%) and independence (60%), and adult-onset caregivers prioritized personality (60%). Almost all patients (93%) would participate in a clinical trial if given the opportunity, but travel to a clinical site could pose a participation barrier for half.

Conclusion:

This study found that there are symptom domains that are relevant across the DRPLA population, but there is heterogeneity within each domain based on the age of symptom onset and disease stage, which has implications for clinical trial design.
Understanding patient, caregiver, and healthcare provider perspectives of the management of long-chain fatty acid oxidation disorders
Authors: Baker Eileen Sullivan , Botham Jennifer , Rechisky Tasia , Romano Evelyn , Garcia Daniel , Berry Susan A.
Published: May 2024

Long-chain fatty acid oxidation disorders (LC-FAODs) are a group of rare, inherited, metabolic disorders that can lead to a wide range of symptoms that predominantly affect organ systems with high energy needs, such as the heart, liver, skeletal muscle, and nervous system. Clinical management primarily consists of close attention to and monitoring of diet and activity and avoidance of prolonged fasting. In addition, patients and caregivers must be alert for signs of life-threatening metabolic decompensation. As a result, LC-FAODs can have significant and wide-ranging impacts on the lives of patients and their caregivers. This article describes the effects of LC-FAODs at different life stages and in the context of the North American healthcare system from the perspective of a group of patients, caregivers, and healthcare providers ( n = 6). We explain how challenges and needs change throughout life. Following an early diagnosis, an adjustment phase occurs during which caregivers may feel overwhelmed by their new roles and deeply concerned for their children’s futures. As children grow, they become more aware of the differences between themselves and their peers, and with increasing independence comes more responsibility for managing their own condition. Major life events, such as new employment and moving house, pose challenges for people of all ages. In addition, it may be difficult to find and connect with qualified and experienced healthcare providers; navigate the health insurance system; and educate and align primary, specialist, and emergency care providers. We propose several strategies to improve the care of patients with LC-FAODs, such as educating local healthcare teams, improving trust between patients/caregivers and healthcare providers, and raising awareness of the challenges faced by patients and caregivers across the different life stages.
Narrowing the Discrepancy in Interobserver Variability With Barrett’s Esophagus With Low-Grade Dysplasia: Will Biomarkers or Risk Testing Help?
Authors: Enke Thomas , Pokala Sridevi K. , Wani Sachin
Published: May 2024

The management of Barrett’s esophagus (BE) with low-grade dysplasia (BE-LGD) remains a unique challenge. Those challenges include high interobserver variability among pathologists, variable natural history of BE-LGD and neoplastic progression, and the lack of established and validated risk prediction tools to guide management of patients with BE-LGD. Current guidelines recommend a patient-centered approach and acknowledge endoscopic eradication therapy and surveillance are acceptable management strategies. Emerging risk assessment tools incorporating clinical, histological, morphological, epigenetic, or molecular features may assist in appropriate stratification. This article reviews the current literature of risk stratification tools in patients with BE-LGD.
Arthroscopic Medial Meniscal Root Repair Using a Novel Re-Tensionable All-Suture Anchor
Authors: Szukics Patrick , Robaina Jose , Ravich Jonas W. , Vargas Luis A. , Yagnik Gautam
Published: May 2024

Background:

Medial meniscal root repairs are devastating injuries that can cause long-term knee problems if not properly addressed. Some common issues when addressing these injuries surgically include the “bungee-cord” effect seen with implants that sit too far from the tibial plateau surface and loss of tension on the sutures after cycling of the knee after the repair. This video will discuss the presentation of a patient with a medial meniscal root repair treated with a novel technique to counteract these aforementioned issues.

Indications:

Based on the patient’s medial meniscal root tear and minimal arthritis seen on radiograph, he was indicated for a meniscal root repair to prevent meniscal extrusion and reinforce normal meniscal hoop stresses to limit progression of his arthritis.

Technique Description:

This technique uses a novel re-tensionable all-suture anchor through a transtibial tunnel with 2 repair sutures through the meniscal root that sits just below the tibial plateau, allowing the surgeon the ability to re-tension the implant after cycling the knee.

Results:

Arthroscopic repair of the medial meniscal root allowed the patient to return to his previous level of activity.

Discussion/Conclusion:

In this case, arthroscopic medial meniscal root repair can yield good results in patients to get them back to their previous level of activity while minimizing the chance of rapid arthritic progression that is typically seen with nonoperative management of these injuries.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Using an Online Assessment Tool to Teach Authentic Assessment to Early Childhood Teacher Candidates
Authors: Rahn Naomi L. , La Croix Leslie , Shin Doohyun L. , Gravil Meg , Chen Ching-I , Hix-Small Hollie , Arora Samita , Grisham Jennifer , Rutland Julie Harp , Chai Zhen , Mickelson Ann M. , Xie Huichao
Published: May 2024

Early childhood teacher candidates (TCs) need preparatory experiences using authentic assessments to inform their instructional practices with rural learners and their families. The shift to virtual field placements in response to COVID-19 restrictions pushed faculty in teacher preparation programs to reimagine how to engage TCs in meaningful experiences using authentic assessments with children and families. This study explores how TCs experienced authentic assessment practices using an online assessment management system, Assessment, Evaluation, and Programming System Interactive (AEPS i), during virtual field experiences. Fifty-five undergraduate and graduate TCs from 11 universities (10 U.S. & 1 international) completed a 45-item survey about their experience. Teacher candidates articulated knowledge and skills aligned with best practices underpinning authentic assessments. The virtual learning environment created opportunities for faculty to reimagine practices for promoting TCs’ understandings of assessment in early childhood special education contexts. We discuss implications for training TCs in rural areas to use authentic assessment.
Dickkopf-1 (DKK1) blockade mitigates osteogenesis imperfecta (OI) related bone disease
Authors: Ko Jih-Yang , Wang Feng-Sheng , Lian Wei-Shiung , Yang Fu-Shine , Chen Jeng-Wei , Huang Po-Hua , Liao Chin-Yi , Kuo Shu-Jui
Published: May 2024

Background

The current treatment of osteogenesis imperfecta (OI) is imperfect. Our study thus delves into the potential of using Dickkopf-1 antisense (DKK1-AS) to treat OI.

Methods

We analysed serum DKK1 levels and their correlation with lumbar spine and hip T-scores in OI patients. Comparative analyses were conducted involving bone marrow stromal cells (BMSCs) and bone tissues from wild-type mice, untreated OI mice, and OI mice treated with DKK1-ASor DKK1-sense (DKK1-S).

Results

Significant inverse correlations were noted between serum DKK1 levels and lumbar spine (correlation coefficient = − 0.679, p = 0.043) as well as hip T-scores (correlation coefficient = − 0.689, p = 0.042) in OI patients. DKK1-AS improved bone mineral density (p = 0.002), trabecular bone volume/total volume fraction (p < 0.001), trabecular separation (p = 0.010), trabecular thickness (p = 0.001), trabecular number (p < 0.001), and cortical thickness (p < 0.001) in OI mice. DKK1-AS enhanced the transcription of collagen 1α1, osteocalcin, runx2, and osterix in BMSC from OI mice (all p < 0.001), resulting in a higher von Kossa-stained matrix area (p < 0.001) in ex vivo osteogenesis assays. DKK1-AS also reduced osteoclast numbers (p < 0.001), increased β-catenin and T-cell factor 4 immunostaining reactivity (both p < 0.001), enhanced mineral apposition rate and bone formation rate per bone surface (both p < 0.001), and decreased osteoclast area (p < 0.001) in OI mice. DKK1-AS upregulated osteoprotegerin and downregulated nuclear factor-kappa B ligand transcription (both p < 0.001). Bone tissues from OI mice treated with DKK1-AS exhibited significantly higher breaking force compared to untreated OI mice (p < 0.001).

Conclusions

Our study elucidates that DKK1-AS has the capability to enhance bone mechanical properties, restore the transcription of osteogenic genes, promote osteogenesis, and inhibit osteoclastogenesis in OI mice.
In silico analysis identified bZIP transcription factors genes responsive to abiotic stress in Alfalfa (Medicago sativa L.)
Authors: Parajuli Atit , Borphukan Bhabesh , Sanguinet Karen A. , Zhang Zhiwu
Published: May 2024

Background

Alfalfa (Medicago sativa L.) is the most cultivated forage legume around the world. Under a variety of growing conditions, forage yield in alfalfa is stymied by biotic and abiotic stresses including heat, salt, drought, and disease. Given the sessile nature of plants, they use strategies including, but not limited to, differential gene expression to respond to environmental cues. Transcription factors control the expression of genes that contribute to or enable tolerance and survival during periods of stress. Basic-leucine zipper (bZIP) transcription factors have been demonstrated to play a critical role in regulating plant growth and development as well as mediate the responses to abiotic stress in several species, including Arabidopsis thaliana, Oryza sativa, Lotus japonicus and Medicago truncatula. However, there is little information about bZIP transcription factors in cultivated alfalfa.

Result

In the present study, 237 bZIP genes were identified in alfalfa from publicly available sequencing data. Multiple sequence alignments showed the presence of intact bZIP motifs in the identified sequences. Based on previous phylogenetic analyses in A. thaliana, alfalfa bZIPs were similarly divided and fell into 10 groups. The physico-chemical properties, motif analysis and phylogenetic study of the alfalfa bZIPs revealed high specificity within groups. The differential expression of alfalfa bZIPs in a suite of tissues indicates that bZIP genes are specifically expressed at different developmental stages in alfalfa. Similarly, expression analysis in response to ABA, cold, drought and salt stresses, indicates that a subset of bZIP genes are also differentially expressed and likely play a role in abiotic stress signaling and/or tolerance. RT-qPCR analysis on selected genes further verified these differential expression patterns.

Conclusions

Taken together, this work provides a framework for the future study of bZIPs in alfalfa and presents candidate bZIPs involved in stress-response signaling.
Coexistence of plasmid-mediated quinolone resistance (PMQR) and extended-spectrum beta-lactamase (ESBL) genes among clinical Pseudomonas aeruginosa isolates in Egypt
Authors: Abdelrahim Soha S. , Hassuna Noha A. , Waly Nancy G. F. M. , Kotb Dalia N. , Abdelhamid Haitham , Zaki Shaimaa
Published: May 2024

Background

Data about the prevalence of plasmid-mediated quinolone resistance (PMQR) and extended-spectrum beta-lactamase (ESBL) production in P. aeruginosa compared to the Enterobacteriaceae family is limited. The availability of limited therapeutic options raises alarming concerns about the treatment of multidrug-resistant P. aeruginosa. This study aimed to assess the presence of PMQR and ESBL genes among P. aeruginosa strains.

Methods

Fifty-six P. aeruginosa strains were isolated from 330 patients with different clinical infections. Phenotypically fluoroquinolone-resistant isolates were tested by PCR for the presence of six PMQR genes. Then, blaTEM, blaSHV, and blaCTX-M type ESBL genes were screened to study the co-existence of different resistance determinants.

Results

Overall, 22/56 (39.3%) of the studied P. aeruginosa isolates were phenotypically resistant to fluoroquinolones. PMQR-producing P. aeruginosa isolates were identified in 20 isolates (90.9%). The acc(6')-Ib-cr was the most prevalent PMQR gene (77.3%). The qnr genes occurred in 72.7%, with the predominance of the qnrA gene at 54.5%, followed by the qnrS gene at 27.3%, then qnrB and qnrC at 22.7%. The qepA was not detected in any isolate. The acc(6')-Ib-cr was associated with qnr genes in 65% of positive PMQR isolates. Significant differences between the fluoroquinolone-resistant and fluoroquinolone-susceptible isolates in terms of the antibiotic resistance rates of amikacin, imipenem, and cefepime (P value < 0.0001) were found. The ESBL genes were detected in 52% of cephalosporin-resistant P. aeruginosa isolates. The most frequent ESBL gene was blaCTX-M (76.9%), followed by blaTEM (46.2%). No isolates carried the blaSHV gene. The acc(6')-Ib-cr gene showed the highest association with ESBL genes, followed by the qnrA gene. The correlation matrix of the detected PMQR and ESBL genes indicated overall positive correlations. The strongest and most highly significant correlation was between qnrA and acc(6')-Ib-cr (r = 0.602) and between qnrA and blaCTX-M (r = 0.519).

Conclusion

A high prevalence of PMQR genes among the phenotypic fluoroquinolone-resistant P. aeruginosa isolates was detected, with the co-carriage of different PMQR genes. The most frequent PMQR was the acc(6')-Ib-cr gene. Co-existence between PMQR and ESBL genes was found, with 75% of PMQR-positive isolates carrying at least one ESBL gene. A high and significant correlation between the ESBL and PMQR genes was detected.
A meta-analysis of photosynthetic efficiency and stress mitigation by melatonin in enhancing wheat tolerance
Authors: Muhammad Ihsan , Ullah Fahim , Ahmad Shakeel , AlMunqedhi Bandar M. , Al Farraj Dunia A , Elshikh Mohamed S , Shen Weijun
Published: May 2024

Background

Our meta-analysis examines the effects of melatonin on wheat under varying abiotic stress conditions, focusing on photosynthetic parameters, chlorophyll fluorescence, leaf water status, and photosynthetic pigments. We initially collected 177 publications addressing the impact of melatonin on wheat. After meticulous screening, 31 published studies were selected, encompassing 170 observations on photosynthetic parameters, 73 on chlorophyll fluorescence, 65 on leaf water status, 240 on photosynthetic pigments.

Results

The analysis revealed significant heterogeneity across studies (I² > 99.90%) for the aforementioned parameters and evidence of publication bias, emphasizing the complex interaction between melatonin application and plant physiological responses. Melatonin enhanced the overall response ratio (lnRR) for photosynthetic rates, stomatal conductance, transpiration rates, and fluorescence yields by 20.49, 22.39, 30.96, and 1.09%, respectively, compared to the control (no melatonin). The most notable effects were under controlled environmental conditions. Moreover, melatonin significantly improved leaf water content and reduced water potential, particularly under hydroponic conditions and varied abiotic stresses, highlighting its role in mitigating water stress. The analysis also revealed increases in chlorophyll pigments with soil drenching and foliar spray, and these were considered the effective application methods. Furthermore, melatonin influenced chlorophyll SPAD and intercellular CO2 concentrations, suggesting its capacity to optimize photosynthetic efficiency.

Conclusions

This synthesis of meta-analysis confirms that melatonin significantly enhances wheat’s resilience to abiotic stress by improving photosynthetic parameters, chlorophyll fluorescence, leaf water status, and photosynthetic pigments. Despite observed heterogeneity and publication bias, the consistent beneficial effects of melatonin, particularly under controlled conditions with specific application methods e.g. soil drenching and foliar spray, demonstrate its utility as a plant growth regulator for stress management. These findings encourage focused research and application strategies to maximize the benefits of melatonin in wheat farming, and thus contributing to sustainable agricultural practices.
Ultrasound guided quadratus lumborum block versus interlaminar epidural block for analgesia in pediatric abdominal surgery: a randomized controlled trial
Authors: Wageh Mohamed , Sultan Mohamed Ahmed , Moawad Hazem El Sayed , Mokbel Ehab Mohamed , Alseoudy Mahmoud Mohammed
Published: May 2024

Background

Although the efficacy and safety of epidural block (EB) are fairly high, complications such as inadvertent dural puncture may limit its use. Ultrasound-guided quadratus lumborum block (QLB) is a relatively new regional technique that provides perioperative somatic and visceral analgesia for pediatric patients. This trial compared the quality of pain relief in pediatric patients undergoing abdominal surgery who received either QLB or EB.

Methods

Patients were randomly allocated into two equal groups: Group E(n = 29): received EB; Group QL(n = 29): received QLB. Both groups were injected with 0.25% bupivacaine (0.5 ml/kg). Assessment of total analgesia consumption was the primary outcome measure, whereas the secondary outcome measures were assessment of postoperative analgesic effect by Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) and time of first analgesic request.

Results

Our study showed that the mean total fentanyl consumption was comparable between both groups(38.67 ± 5.02 and 36.47 ± 5.13 µg in the E and QL groups, respectively,P = 0.246). Only five patients did not require rescue analgesia (3 in the E group,2 in the QL group,P = 0.378). The mean duration of analgesia showed no significant difference between the two groups (9.9 ± 1.58 and 11.02 ± 1.74 h in the E and QL groups, respectively,P = 0.212). Evaluation of CHEOPS score values immediately in PACU and for the initial 24 h following operation showed no significant difference between the two study groups(P > 0.05).

Conclusion

QLB can achieve analgesic effects comparable to those of EB as a crucial part of multimodal analgesia in children undergoing abdominal surgeries.

Clinical trial registration number

PACTR202203906027106.
Widespread use of proton pump inhibitors or potassium-competitive acid blocker has changed the status of gastrointestinal bleeding in patients with ischemic heart disease: real-world data from high volume centers
Authors: Sasaki Shun , Ota Kazuhiro , Sanomura Makoto , Mori Yosuke , Tanaka Hironori , Hakoda Akitoshi , Sugawara Noriaki , Iwatsubo Taro , Hirata Yuki , Kakimoto Kazuki , Morita Hideaki , Nagamatsu Wataru , Hoshiga Masaaki , Takeuchi Toshihisa , Higuchi Kazuhide , Nishikawa Hiroki
Published: May 2024

Background

Although proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) are useful in peptic ulcer prevention, their efficacy in preventing other gastrointestinal bleeding remains unclear. This study aimed to identify the status of gastrointestinal bleeding in the modern era when PPIs are widely used.

Methods

This study included patients who underwent percutaneous coronary intervention (PCI) between 2018 and 2019 at two high-volume centers. Patients were categorized based on whether they experienced gastrointestinal bleeding within 2 years of PCI into groups A (patients who experienced gastrointestinal bleeding within 2 years after PCI) and B (patients who did not experience gastrointestinal bleeding).

Results

Groups A and B included 21 (4.1%) and 494 (95.9%) patients, respectively (a total of 515 patients). Age at the initial PCI (77.8±2.4 and 72.0±0.5 years in groups A and B, respectively; p = 0.02), weight (53.8±3.2 and 61.8±0.7 kg in groups A and B, respectively; p = 0.01), and concomitant warfarin use (14.3% and 2.0% in groups A and B, respectively; p = 0.0005) were significantly different between the groups. The high bleeding risk rate (90.5% and 47.6% in groups A and B, respectively; p = 0.0001) was significantly different between the groups. A total of 95.9% of patients were taking PPIs or PCAB without significant differences between the groups. However, only one patient, who was taking steroids, had a gastric ulcer during PCAB treatment.

Conclusions

Acid-related upper gastrointestinal bleeding is largely controlled by PPIs in post-PCI patients. Furthermore, the risk factors for non-acid-related bleeding include older age, lower weight, and concomitant warfarin use.
Sarcopenic obesity in nursing home residents: a multi-center study on diagnostic methods and their association with instrumental activities of daily living
Authors: Tang Huiyu , Li Runjie , Li Ruicen , Lian Rongna , Chen Xiaoyan , Jiang Wenhua , Jiang Jiaojiao , Yang Ming
Published: May 2024

Background

Sarcopenic obesity (SO) in nursing home residents is rarely studied. We aimed to evaluate and compare the prevalence and consistency of different SO diagnostic methods and to investigate which criterion demonstrated a stronger association with instrumental activities of daily living (IADL) disability.

Methods

We consecutively recruited older adults aged ≥ 60 years, residing in 15 nursing homes in Zigong City, China. Sarcopenia obesity was defined according to the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity criteria (SOESPEN), recommending skeletal muscle mass (SMM) adjusted by body weight (SMM/W) to identify low muscle mass. Further, we adapted ESPEN criteria (SOESPEN−M) by employing SMM adjusted by body mass index (SMM/BMI).

Results

We included 832 participants (median age 73.0 years, 296 women). The prevalence of SOESPEN and SOESPEN−M was 43.5% and 45.3%, respectively. SOESPEN showed good consistency with SOESPEN−M (Cohen’s kappa = 0.759). More than one-third of participants in the normal weight group were diagnosed with SOESPEN or SOESPEN−M. Even within the underweight group, the prevalence of SOESPEN and SOESPEN−M was 8.9% and 22.2%, respectively. Participants with IADL disability had significantly lower SMM/W and SMM/BMI, but higher fat mass percentage of body weight (FM%) than participants without IADL disability. After full adjustment for potential confounders, SOESPEN−M (OR 1.68, 95% CI 1.21 to 2.32), but not SOESPEN (OR 1.28, 95% CI 0.93 to 1.75), remained significantly associated with IADL disability.

Conclusions

Both SOESPEN and SOESPEN−M showed a high prevalence among nursing home residents, even among individuals with underweight or normal weight. While SOESPEN had a good consistency with SOESPEN−M, only SOESPEN−M was independently associated with IADL disability. Screening and diagnosis of SO should be conducted in nursing home residents irrespective of BMI.
Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team—a multicenter phase II trial
Authors: Liu Wen-Yang , Tang Yuan , Li Ning , Tang Yu , Cheng Yun-Jie , Yang Lin , Fang Hui , Lu Ning-Ning , Qi Shu-Nan , Chen Bo , Wang Shu-Lian , Song Yong-Wen , Liu Yue-Ping , Li Ye-Xiong , Liu Zheng , Liang Jian-Wei , Pei Wei , Wang Xi-Shan , Zhang Hai-Zeng , Wang Jun , Zhou Hai-Tao , Jin Jing
Published: May 2024

Background

The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as “fit” by comprehensive geriatric assessment (CGA).

Methods

A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of “fit” (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22).

Results

One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47).

Conclusion

This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA.

Trial registration

The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).
Seroprevalence and placental transfer of SARS-CoV-2 antibodies in unvaccinated pregnant women
Authors: Vercoutere An , Zina Mbiton Joel , Telis Meltem , Goffard Jean-Christophe , Boulvain Michel , de Doncker Loïc , Derisbourg Sara , Houben Sylvie , Delforge Marie-Luce , Daelemans Caroline , Kelen Dorottya
Published: May 2024

Purpose

Pregnant women are at risk of severe SARS-CoV-2 infection, potentially leading to obstetric and neonatal complications. Placental transfer of antibodies directed to SARS-CoV-2 may be protective against neonatal COVID-19, but this remains to be studied. We aimed to determine the seroprevalence of SARS-CoV-2 antibodies in a population of unvaccinated pregnant women and to determine the placental transfer of these antibodies.

Methodology

A total of 1197 unvaccinated women with mostly unknown pre-study SARS-CoV-2 infection status, were tested at delivery for SARS-CoV-2 spike protein IgG antibodies during the first year of the pandemic. Umbilical cord samples were collected and assessed for seropositivity if the mother was seropositive. Maternal characteristics, pregnancy and neonatal outcomes and data on SARS-CoV-2 infection were extracted from medical records.

Results

Specific IgG were detected in 258 women (21.6%). A significant placental transfer to the newborn was observed in 81.3% of cases. The earlier in the 2nd and 3rd trimesters that the mother had contracted the disease and the more symptomatic she was, the greater the likelihood of transplacental transfer of IgG to her newborn.

Conclusion

Approximately one in five women had detectable anti-SARS-CoV-2 spike protein IgG antibodies at delivery during the first year of the pandemic, and these antibodies were significantly transferred to their fetuses. This research provides further evidence to better understand the dynamics of the placental transfer of SARS-CoV-2 IgG antibodies from mothers to their newborns, which is necessary to improve vaccination strategies.
Modelling respiratory syncytial virus age-specific risk of hospitalisation in term and preterm infants
Authors: Giannini Fiona , Hogan Alexandra B. , Sarna Mohinder , Glass Kathryn , Moore Hannah C.
Published: May 2024

Background

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control.

Methods

We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000–2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection.

Results

The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants.

Conclusions

The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV.
Predicting major adverse cardiovascular events within 3 years by optimization of radiomics model derived from pericoronary adipose tissue on coronary computed tomography angiography: a case-control study
Authors: Zhang Rong-rong , You Hong-rui , Geng Ya-yuan , Li Xiao-gang , Sun Yu , Hou Jie , Ji Lian-chang , Shi Jing-long , Zhang Li-bo , Yang Ben-qiang
Published: May 2024

Background

Coronary inflammation induces changes in pericoronary adipose tissue (PCAT) can be detected by coronary computed tomography angiography (CCTA). Our aim was to investigate whether different PCAT radiomics model based on CCTA could improve the prediction of major adverse cardiovascular events (MACE) within 3 years.

Methods

This retrospective study included 141 consecutive patients with MACE and matched to patients with non-MACE (n = 141). Patients were randomly assigned into training and test datasets at a ratio of 8:2. After the robust radiomics features were selected by using the Spearman correlation analysis and the least absolute shrinkage and selection operator, radiomics models were built based on different machine learning algorithms. The clinical model was then calculated according to independent clinical risk factors. Finally, an overall model was established using the radiomics features and the clinical factors. Performance of the models was evaluated for discrimination degree, calibration degree, and clinical usefulness.

Results

The diagnostic performance of the PCAT model was superior to that of the RCA-model, LAD-model, and LCX-model alone, with AUCs of 0.723, 0.675, 0.664, and 0.623, respectively. The overall model showed superior diagnostic performance than that of the PCAT-model and Cli-model, with AUCs of 0.797, 0.723, and 0.706, respectively. Calibration curve showed good fitness of the overall model, and decision curve analyze demonstrated that the model provides greater clinical benefit.

Conclusion

The CCTA-based PCAT radiomics features of three major coronary arteries have the potential to be used as a predictor for MACE. The overall model incorporating the radiomics features and clinical factors offered significantly higher discrimination ability for MACE than using radiomics or clinical factors alone.
Characteristics of recurrence in area postrema-onset NMO spectrum disorder - a retrospective cohort study
Authors: Zhang Xianxing , Wu Jin , Lin Jingyu , Lin Shifang , Lin Aiyu
Published: May 2024

Background

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory autoimmune disease with high risk of recurrence and disability, the treatment goal is a recurrence free state. Area postrema (AP) is one of the most common involved area of NMOSD, which may have a particular significance in the pathogenesis of NMOSD and clinical heterogeneity. Our study is to investigate the clinical and recurrent characteristics AP onset NMOSD patients.

Methods

A retrospective study was done in a cohort of 166 AQP4-IgG seropositive NMOSD patients which were identified by the 2015 IPND criteria. The patients were divided into AP onset (APO-NMOSD) group and non-AP onset (NAPO-NMOSD) group based on the initial episode location. Clinical features and recurrence differences of two groups were compared.

Results

The APO-NMOSD group and NAPO-NMOSD group had a population ratio of 24:142. APO-NMOSD patients were younger (34.6y VS 42.3y, P = 0.013), had lower EDSS at first episode (0.7 VS 4.2, p = 0.028) and last follow up (1.9 VS 3.3, p = 0.001), more likely to have multi-core lesions at the first attack (33.3% VS 9.2%, P = 0.001). Also, they had a higher annual recurrence rate (0.4 ± 0.28 VS 0.19 ± 0.25, P = 0.012). In natural course NMOSD patients without immunotherapy, APO-NMSOD had a shorter time of first relapse (P < 0.001) and higher annual recurrence rate (0.31 ± 0.22 VS 0.16 ± 0.26, P = 0.038) than NAPO-NMOSD. APO-NMOSD group also have a higher risk of having the first relapsing compared to optic neuritis onset-NMOSD (HR 2.641, 95% CI 1.427–4.887, p = 0.002) and myelitis onset-NMOSD group (HR 3.593, 95% CI 1.736–7.438, p = 0.001). Compared to NAPO-NMOSD, APO-NMOSD has a higher likelihood of brainstem recurrence (28.6% vs. 4.7%, p<0.001) during the first recurrence, while NAPO-NMOSD is more susceptible to optic nerve involvement (10.7% vs. 41.1%, p = 0.01).

Conclusion

AQP4-IgG seropositive NMOSD patients with AP onset are youngers and have higher risk of recurrence. Clinicians should pay attention to AP damage in NMOSD, as it indicates a potential risk of recurrence.

Trial registration

Retrospectively registered.
Psychiatric implications of anti-seizure medications in epileptic population
Authors: Khalid Bushra , Waqar Zaid , Khan Soban , Ali Ijaz , Afzal Naheed , Irfan Anum , Malik Waleed , Muhammad Adil Malik , Saddiqa Amina , Khalil Maryam , Munawar Zeeshan
Published: May 2024

Background and objective

Epilepsy is a prevalent neurological disorder that affects a significant number of individuals globally. This condition is associated with a high occurrence of psychiatric comorbidities, which can significantly affect the quality of life of individuals affected. The aim of this study was to investigate the association between antiseizure therapies and the likelihood of psychiatric comorbidities in individuals with epilepsy.

Methodology

Data for this study was gathered from the Neurology referral center in Islamabad, Pakistan. A standardized questionnaire was utilized to gather data from 120 individuals diagnosed with epilepsy. The survey consisted of inquiries regarding the management of seizures, the utilization of anti-seizure medications, and the presence of psychiatric comorbidities. The data was analyzed using the Statistical Package for the Social Sciences (SPSS).

Results

The findings indicated that individuals who were using multiple antiseizure medications had a notably higher likelihood of having psychiatric comorbidities in comparison to those who were on mono therapy (p = 0.010). suggests that patients with unsuccessful seizure control are more probable to have psychiatric comorbidities as compared to those with good seizure control (p = 0.029).

Conclusion

To conclude poor seizure control and poly therapy are associated with increased risk of psychiatric comorbidities.
Spinal cord stimulation for postural abnormalities in Parkinson’s disease: 1-year prospective pilot study
Authors: Zhou Liche , Chen Fangzheng , Pan Yixin , Wang Linbin , Xu Lu , Huang Peng , Wang Lijun , Luo Ningdi , Li Puyu , Li Dianyou , Liu Jun
Published: May 2024

Background

Postural abnormalities (PA) are common in the advanced stages of Parkinson’s disease (PD), but effective therapies are lacking. A few studies suggested that spinal cord stimulation (SCS) could be a potential therapy whereas its effect is still uncertain. We aimed to investigate whether SCS had potential for benefiting PD patients with PA.

Methods

T8-12 SCS was operated on six PD patients with PA and all patients were followed for one year. Evaluations were made before and after SCS. Moreover, three patients were tested separately with SCS on-state and off-state to confirm the efficacy of SCS.

Results

Improvements in lateral trunk flexion degree, anterior thoracolumbar flexion degree and motor function were found after SCS. The improvements diminished while SCS was turned off.

Conclusions

Lower thoracic SCS may be effective for improving PA in PD patients, but further studies are needed to confirm this conclusion.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1900024326, Registered on 6th July 2019; https://www.chictr.org.cn/showproj.aspx?proj=40835.
UCHL5 promotes hepatocellular carcinoma progression by promoting glycolysis through activating Wnt/β-catenin pathway
Authors: Wan Baishun , Cheng Ming , He Tao , Zhang Ling
Published: May 2024

Background

Hepatocellular carcinoma (HCC) is highly malignant with a dismal prognosis, although the available therapies are insufficient. No efficient ubiquitinase has been identified as a therapeutic target for HCC despite the complicating role that of proteins ubiquitination plays in the malignant development of HCC.

Methods

The expression of ubiquitin carboxyl terminal hydrolase L5 (UCHL5) in HCC tumor tissue and adjacent normal tissue was determined using the cancer genome atlas (TCGA) database and was validated using real-time quantitative polymerase chain reaction (RT-qRCR), Western blot and immunohistochemistry (IHC), and the relation of UCHL5 with patient clinical prognosis was explored. The expression of UCHL5 was knocked down and validated, and the effect of UCHL5 on the biological course of HCC was explored using cellular assays. To clarify the molecular mechanism of action of UCHL5 affecting HCC, expression studies of Adenosine triphosphate adenosine triphosphate (ATP), extracellular acidification (ECAR), and glycolysis-related enzymes were performed. The effects of UCHL5 on β-catenin ubiquitination and Wnt signaling pathways were explored in depth and validated using cellular functionalities. Validation was also performed in vivo.

Results

In the course of this investigation, we discovered that UCHL5 was strongly expressed in HCC at both cellular and tissue levels. The prognosis of patients with high UCHL5 expression is considerably worse than that of those with low UCHL5 expression. UCHL5 has been shown to increase the degree of glycolysis in HCC cells with the impact of stimulating the proliferation and metastasis of HCC cells in both in vivo and in vitro. UCHL5 downregulates its degree of ubiquitination by binding to β-catenin, which activates the Wnt/β-catenin pathway and accelerates HCC cell glycolysis. Thereby promoting the growth of the HCC.

Conclusions

In summary, we have demonstrated for the first time that UCHL5 is a target of HCC and promotes the progression of hepatocellular carcinoma by promoting glycolysis through the activation of the Wnt/β-catenin pathway. UCHL5 may thus serve as a novel prognostic marker and therapeutic target for the treatment of HCC.
Association between dietary behavior and puberty in girls
Authors: Du Yiming , Yan Wu , Bigambo Francis Manyori , Zhou Qiaoli , Ma Chenguang , Gu Wei , Wang Xu
Published: May 2024

Introduction

Over the decades the trends of early onset of puberty have been observed in children, particularly in girls. Research evidence has reported diet to be among the most important risk factors for puberty onset. This study evaluated the association between dietary behavior and puberty in girls.

Methods

We enrolled 201 girls with the main complaints of breast development as the cases at the Endocrine Department of Nanjing Children's Hospital. The cases were divided into breast development with central priming and breast development without central priming groups and were matched with 223 normal health girls with no breast development (control group). We used the modified Child Eating Behavior Questionnaire (CEBQ) to conduct a face-to-face interview about dietary behavior. Sample t-test or Mann Whitney U test or Chi-square test, the analysis of variance or Kruskal Wallis test, and least significant difference (LSD) were used to compare differences between the groups, Bonferroni was used to correct the p-value, and logistic regression was used to analyze risk factors for puberty onset.

Results

A total of 424 girls participated in this study, among them, 136 were cases with breast development with central priming, 65 were cases with breast development without central priming, and 223 were normal health girls with no breast development. Age of the participants ranged from 4.5 to 9.3 years. There were significant differences in food response (p < 0.001), dietary restriction (p < 0.001), frequencies of vegetable intake (χ2 = 8.856, p = 0.012), drinking milk (χ2 = 23.099, p = 0.001), and borderline statistical difference in a total score of unhealthy dietary behavior (p = 0.053) among the cases and controls. However, in the post hoc analysis, these dietary behaviors were significant differences between the girls with breast development with central priming and the control groups. Moreover, girls in the breast development with central priming group had significantly higher bone age (BA), uterine body length, ovarian volume, basal luteinizing hormone (LH), basal follicle-stimulating hormone (FSH), peak LH, peak FSH, estradiol (E2), and free triiodothyronine (FT3) compared to those in the breast development without central priming group. In the multivariate logistic regression, only uterine body length was associated with increased risk of breast development with central priming (OR = 1.516, 95%CI: 1.243–1.850).

Conclusion

There were significant differences in dietary behaviors among girls with breast development with central priming and normal health girls with no breast development, and uterine body length was associated with an increasing risk of breast development with central priming among girls with breast development.
A complex systems perspective on chronic aggression and self-injury: case study of a woman with mild intellectual disability and borderline personality disorder
Authors: Hulsmans Daan H. G. , Otten Roy , Poelen Evelien A. P. , van Vonderen Annemarie , Daalmans Serena , Hasselman Fred , Olthof Merlijn , Lichtwarck-Aschoff Anna
Published: May 2024

Background

Challenging behaviors like aggression and self-injury are dangerous for clients and staff in residential care. These behaviors are not well understood and therefore often labeled as “complex”. Yet it remains vague what this supposed complexity entails at the individual level. This case-study used a three-step mixed-methods analytical strategy, inspired by complex systems theory. First, we construed a holistic summary of relevant factors in her daily life. Second, we described her challenging behavioral trajectory by identifying stable phases. Third, instability and extraordinary events in her environment were evaluated as potential change-inducing mechanisms between different phases.

Case presentation

A woman, living at a residential facility, diagnosed with mild intellectual disability and borderline personality disorder, who shows a chronic pattern of aggressive and self-injurious incidents. She used ecological momentary assessments to self-rate challenging behaviors daily for 560 days.

Conclusions

A qualitative summary of caretaker records revealed many internal and environmental factors relevant to her daily life. Her clinician narrowed these down to 11 staff hypothesized risk- and protective factors, such as reliving trauma, experiencing pain, receiving medical care or compliments. Coercive measures increased the chance of challenging behavior the day after and psychological therapy sessions decreased the chance of self-injury the day after. The majority of contemporaneous and lagged associations between these 11 factors and self-reported challenging behaviors were non-significant, indicating that challenging behaviors are not governed by mono-causal if-then relations, speaking to its complex nature. Despite this complexity there were patterns in the temporal ordering of incidents. Aggression and self-injury occurred on respectively 13% and 50% of the 560 days. On this timeline 11 distinct stable phases were identified that alternated between four unique states: high levels of aggression and self-injury, average aggression and self-injury, low aggression and self-injury, and low aggression with high self-injury. Eight out of ten transitions between phases were triggered by extraordinary events in her environment, or preceded by increased fluctuations in her self-ratings, or a combination of these two. Desirable patterns emerged more often and were less easily malleable, indicating that when she experiences bad times, keeping in mind that better times lie ahead is hopeful and realistic.