bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrent, non-traumatic, non-exertional rhabdomyolysis after immunologic stimuli in a healthy adolescent female: a case report
Authors: Katz Jason , Labilloy Anatalia , Lee Andrew 
Published: August 2022

Abstract
Background
Dysferlinopathy refers to a heterogenous group of autosomal recessive disorders that affect a skeletal muscle protein called dysferlin. These mutations are associated with limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, asymptomatic hyperCKemia, and distal myopathy with anterior tibial onset.

Case presentation
A 16 year old female presented with myalgia, weakness and dark urine one week after her second BNT162b2 mRNA (Pfizer) vaccine. Initial serum creatine kinase (CK) was measured at 153,000 IU/L, eventually up-trending to over 200,000 IU/L. However, stable renal function precluded hemodialysis allowing discharge after 10 days of intravenous (IV) hydration and alkaline diuresis.
Just two years prior to the current presentation, the patient was hospitalized following Group A Streptococcal pharyngitis infection complicated by rhabdomyolysis. She presented with fatigue, lower extremity weakness, and dark oliguria with CK measuring 984,800 IU/L. IV hydration was attempted however hemodialysis was ultimately required throughout her 24-day hospital stay. Her episode was presumed to be idiopathic and no further work-up was performed at that time.
During the patient’s current hospitalization, she reported similar symptomology (myalgias and weakness) following her first quadrivalent Gardasil vaccine at age 11. No hospitalization was required at that time. A comprehensive workup was now initiated while the patient was being treated for her suspected second or third non-exertional, non-traumatic rhabdomyolysis. Rheumatologic, metabolic, infectious, and endocrinologic workup were all unremarkable. Patient eventually had whole exome sequencing performed which revealed a heterozygous pathogenic variant in the DYSF gene (DYSF c.2643 + 1G > A) encoding dysferlin. No clinically significant sequelae occurred thus far.

Conclusions
While there have been reports of symptomatic heterozygote carriers of dysferlinopathies, to our knowledge none have been associated with recurrent rhabdomyolysis after immunogenic stimuli. This unique case presentation highlights the importance of a multi-disciplinary care team, the utility of modern whole-exome gene sequencing, and the future challenges of balancing vaccine risk vs benefit.
Application for simulating public health problems during floods around the Loei River in Thailand: the implementation of a geographic information system and structural equation model
Authors: Boonnuk Tanunchai , Poomphakwaen Kirati , Kumyoung Natchareeya 
Published: August 2022

Abstract
Background
Floods cause not only damage but also public health issues. Developing an application to simulate public health problems during floods around the Loei River by implementing geographic information system (GIS) and structural equation model (SEM) techniques could help improve preparedness and aid plans in response to such problems in general and at the subdistrict level. As a result, the effects of public health problems would be physically and mentally less severe.

Methods
This research and development study examines cross-sectional survey data. Data on demographics, flood severity, preparedness, help, and public health problems during floods were collected using a five-part questionnaire. Calculated from the population proportion living within 300 m of the Loei River, the sample size was 560 people. The participants in each subdistrict were recruited proportionally in line with the course of the Loei River. Compared to the empirical data, the data analysis examined the causal model of public health problems during floods, flood severity, preparedness, and help. The standardized factor loadings obtained from the SEM analysis were substituted as the loadings in the equations for simulating public health problems during floods.

Results
The results revealed that the causal model of public health problems during floods, flood severity, preparation, and help agreed with the empirical data. Flood severity, preparedness, and aid (χ2 = 479.757, df = 160, p value <.05, CFI = 0.985, RMSEA = 0.060, χ2/df = 2.998) could explain 7.7% of public health problems. The computed values were applied in a GIS environment to simulate public health problem situations at the province, district, and subdistrict levels.

Conclusions
Flood severity and public health problems during floods were positively correlated; in contrast, preparedness and help showed an inverse relationship with public health problems. A total of 7.7% of the variance in public health problems during floods could be predicted. The analysed data were assigned in the GIS environment in the developed application to simulate public health problem situations during floods.
Comparison of Ma-Griffith combined with a minimally invasive small incision to a modified suture technique for the treatment of acute achilles tendon ruptures
Authors: Jun Li , Hao Yu , Junfeng Zhan , Jisen Zhang , Xinzhong Xu , Yunfeng Yao , Dasheng Tian , Jia Xie 
Published: August 2022

Abstract
Background
The Achilles tendon is the strongest tendon in the human body, although it is also prone to injury and rupture. Currently, the best treatment method for acute Achilles tendon rupture remains controversial. The aim of this study was to compare the efficacy of the Ma-Griffith method combined with a minimally invasive small incision (M-G/MISI) with the modified suture technique (MST).

Methods
We conducted a retrospective review of the medical records of all patients who underwent treatment for acute Achilles tendon rupture between January 2012 and January 2020 at our hospital. Demographic characteristics, operative details, and postoperative complications were recorded, and data were statistically analyzed to compare the treatment efficacy of the two operative methods.

Results
A total of 67 patients were enrolled in the study, 34 of whom underwent M-G/MISI treatment, and 33 of whom underwent MST treatment. The intraoperative blood loss in the M-G/MISI group (16.47 ± 13.23 ml) was significantly lower than that in the MST group (34.55 ± 13.01 ml), and the difference was statistically significant (P ˂0.001). The incision in the M-G/MISI group (3.79 ± 1.81 cm) was significantly shorter than that in the MST group (5.79 ± 1.00 cm), and the difference was statistically significant (P˂0.001). The Achilles tendon rupture score and the American Orthopedic Foot and Ankle Society (AOFAS) score were higher than those of the MST group at the sixth month after the operation (P˂0.001). Postoperatively, there was 1 case of traumatic Achilles tendon rupture in the M-G/MISI group and 1 case each of infection and deep vein thrombosis in the modified suture group.

Conclusions
Compared with the MST group, the M-G/MISI group had better Achilles tendon and ankle function scores at 6 months postoperatively, and less bleeding and shorter incisions. M-G/MISI is less invasive than MST.
Risk factors predicting residual lesion in subsequent hysterectomy following cold knife conization (CKC) for high-grade squamous intraepithelial lesion (HSIL)
Authors: Zeng Yong , Jiang Tao , Zheng Yahong , Yang Jing , Wei Hua , Yi Cunjian , Liu Yan , Chen Keming 
Published: August 2022

Abstract
Objective
To determine risk factors predicting residual lesion in a subsequent hysterectomy follow a cold knife conization (CKC) for high-grade squamous intraepithelial lesion (HSIL).

Method
Between January 2010 and December 2021, a total of 740 patients who underwent a hysterectomy within 3 months after CKC for HSIL were included in this study. We analyzed their demographic features and pathological parameters. A logistic regression model was used to analyze the relationship between parameters and residual lesion in subsequent hysterectomy specimens.

Results
104 (14.1%) had residual lesion in the hysterectomy specimen, 3 patients with microinvasive carcinoma. The rate of residual lesion in patients with positive endocervical margin was 31.3%, with positive ectocervical margin was 15.3%, with positive combine margin was 38.6%. In multivariate analysis, positive margin (OR 4.015; 95% CI 2.526–6.381; P < 0.001), glandular involvement (OR 3.484; 95% CI 1.457–8.330; P = 0.005), HPV16/18 infection (OR 2.804; 95% CI 1.705–4.611; P < 0.001) and multiple HR-HPV infection (OR 1.813; 95% CI 1.130–2.909; P < 0.014) were independent risk factors for residual lesion. The AUC calculated by logistic regression model was 0.78.

Conclusion
Positive margin, positive glandular involvement, HPV16/18 and multiple HR-HPV infection were independent high risk factors of residual lesion in a subsequent hysterectomy following CKC for HSIL.
Understanding medical students’ transformative experiences of early preclinical international rural placement over a 20-year period
Authors: Malau-Aduli Bunmi S. , Jones Karina , Smith Amy M. , Sen Gupta Tarun , Hays Richard B. 
Published: August 2022

Abstract
Introduction
Rural placements are an important component of rural medical education programs seeking to develop rural practice pathways for medical students. These placements are usually domestic, but James Cook University in Australia developed an international rural placement program in the first half of the medical course that was funded through bursaries. This study explores how the international rural placement helped to shape the lives (personal development and learning) of the participants, using Transformational Learning Theory as a framework for identifying and describing the transformational elements, process and impact of the program.

Methods
Sixty-five students received a bursary for an international rural placement between 2001–2019. All were contacted by email and invited to participate in a short survey and a follow-up interview. Fifteen participants agreed and twelve were able to participate in individual semi-structured interviews which were recorded, transcribed and analysed using inductive thematic analysis.

Results
Participants reported that the bursary provided a “once in a lifetime opportunity” to “experience eye-opening and culturally rich difference”. Nonetheless, some elements of the placement experience presented disorientating dilemmas that triggered deep reflections and shifts in perceptions. The bursary recipients realised that “being open-minded” allowed them “enjoy good company”. They were also able to assume “outsider view which allowed reassessment of their own country” and the “isolation experiences gingered desire to right health wrongs”. The triggers and mental shifts had significant impact on the bursary recipients and fostered the development of “inspirational new horizons” based on an appreciation of the “value of rural practice” and “role-modelling for life-long learning.” These findings are consistent with Transformational Learning Theory.

Conclusion
Participants in this study reported meaningful and strongly positive impacts from the experiences gained during an international rural clinical placement early in their course. They described transformative experiences which appear to contribute strongly to personal development. This finding supports maintaining opportunities for international experiences during rurally-oriented medical programs as these may impact longer term career choice.
Livoneca redmanii Leach, 1818 (Cymothoidae) a parasitic isopod infesting the gills of the European seabass, Dicentrarchus labrax (Linnaeus, 1758): morphological and molecular characterization study
Authors: Abdallah Ebtsam Sayed Hassan , Hamouda Awatef Hamed 
Published: August 2022

Abstract
Background
Prevalence, morphology, and molecular characteristics of isopodiosis in the European seabass, Dicentrarchus labrax, in Egypt were assessed using light and electron microscopy and polymerase chain reaction targeting the mitochondrial COI (cytochrome oxidase c) gene.

Results
Adult parasites were found mainly in the branchial cavity between gill arches and to a lesser extent in the buccal cavity. They were morphologically identified as the Cymothoidae Livoneca redmanii Leach, 1818 (Crustacea: Isopoda). Obviously, a 23% prevalence rate of isopods was reported in D. labrax from Egyptian Mediterranean waters. Destructive and degenerative necrotic alterations with complete sloughing of gill lamellae of the infested fish were observed. DNA sequencing of the mitochondrial COI gene confirmed the identification of the parasite which was deposited in the GenBank under accession numbers MW600099, MZ208984, and MZ208985. Furthermore, the phylogenetic analysis demonstrated that parasites emerged from a monophyletic clade closely affiliated with L. redmanii and were clearly distinguished from other isopod genospecies.

Conclusion
The present investigation addresses L. redmanii infestation in D. labrax in Egypt and affirmed morphological properties via the scanning electron microscopy (SEM) and molecular characteristics of this isopod species. The drastic effects of this parasite on the infected fish were proven both clinically and histopathologically.
Genetic diversity of porcine reproductive and respiratory syndrome virus and evaluation of three one-step real-time RT-PCR assays in Korea
Authors: Shin Go-Eun , Park Ji-Young , Lee Kyoung-Ki , Ko Mi-Kyeong , Ku Bok-Kyung , Park Choi-Kyu , Jeoung Hye-Young 
Published: August 2022

AbstractBackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) has caused huge economic losses in the global swine industry. Frequent genetic variations in this virus cause difficulties in controlling and accurately diagnosing PRRSV.MethodsIn this study, we investigated the genetic characteristics of PRRSV-1 and PRRSV-2 circulating in Korea from January 2018 to September 2021 and evaluated three one-step real-time reverse transcription polymerase chain reaction (RT-PCR) assays.ResultsA total of 129 lung samples were collected, consisting of 47 samples for PRRSV-1, 62 samples for PRRSV-2, and 20 PRRSV-negative samples. Nucleotide sequence analysis of open reading frames (ORFs) 5, ORF6, and ORF7 genes from PRRSV samples showed that PRRSV-1 belonged to subgroup A (43/47, 91.49%) and subgroup C (4/47, 8.51%), whereas PRRSV-2 was classified as lineage 1 (25/62, 40.32%), Korean lineage (Kor) C (13/62, 20.97%), Kor B (10/62, 16.13%), lineage 5 (9/62, 14.52%), and Kor A (5/62, 8.06%). Amino acid sequence analysis showed that the neutralizing epitope and T cell epitope of PRRSV-1, and the decoy epitope region and hypervariable regions of PRRSV-2 had evolved under positive selection pressure. In particular, the key amino acid substitutions were found at positions 102 and 104 of glycoprotein 5 (GP5) in some PRRSV-2, and at positions 10 and 70 of membrane protein (M) in most PRRSV-2. In addition, one-step real-time RT-PCR assays, comprising two commercial tests and one test recommended by the World Organization for Animal Health (OIE), were evaluated.ConclusionThe results revealed that two of the real-time RT-PCR assays had high sensitivities and specificities, whereas the real-time RT-PCR assay of the OIE had low sensitivity due to mismatches between nucleotides of Korean PRRSVs and forward primers. In this study, we genetically characterized recent PRRSV occurrences and evaluated three one-step real-time RT-PCR assays used in Korea.
Do Health Technology Assessment organisations consider manufacturers’ costs in relation to drug price? A study of reimbursement reports
Authors: Enzing Joost J. , Knies Saskia , Engel Jop , IJzerman Maarten J. , Sander Beate , Vreman Rick , Boer Bert , Brouwer Werner B. F. 
Published: August 2022

Abstract
Introduction
Drug reimbursement decisions are often made based on a price set by the manufacturer. In some cases, this price leads to public and scientific debates about whether its level can be justified in relation to its costs, including those related to research and development (R&D) and manufacturing. Such considerations could enter the decision process in collectively financed health care systems. This paper investigates whether manufacturers’ costs in relation to drug prices, or profit margins, are explicitly mentioned and considered by health technology assessment (HTA) organisations.

Method
An analysis of reimbursement reports for cancer drugs was performed. All relevant Dutch HTA-reports, published between 2017 and 2019, were selected and matched with HTA-reports from three other jurisdictions (England, Canada, Australia). Information was extracted. Additionally, reimbursement reports for three cases of expensive non-oncolytic orphan drugs prominent in pricing debates in the Netherlands were investigated in depth to examine consideration of profit margins.

Results
A total of 66 HTA-reports concerning 15 cancer drugs were included. None of these reports contained information on manufacturer’s costs or profit margins. Some reports contained general considerations of the HTA organisation which related prices to manufacturers’ costs: six contained a statement on the lack of price setting transparency, one mentioned recouping R&D costs as a potential argument to justify a high price. For the case studies, 21 HTA-reports were selected. One contained a cost-based price justification provided by the manufacturer. None of the other reports contained information on manufacturer’s costs or profit margins. Six reports contained a discussion about lack of transparency. Reports from two jurisdictions contained invitations to justify high prices by demonstrating high costs.

Conclusion
Despite the attention given to manufacturers’ costs in relation to price in public debates and in the literature, this issue does not seem to get explicit systematic consideration in the reimbursement reports of expensive drugs.
Chronic allergic lung inflammation negatively influences neurobehavioral outcomes in mice
Authors: Kanaya Akihiro , Yang Mu , Emala Charles , Mikami Maya 
Published: August 2022

Abstract
Background
Asthma is a major public health problem worldwide. Emerging data from epidemiological studies show that allergies and allergic diseases may be linked to anxiety, depression and cognitive decline. However, little is known about the effect of asthma, an allergic lung inflammation, on cognitive decline/behavioral changes. Therefore, we investigated the hypothesis that allergic lung inflammation causes inflammation in the brain and leads to neurobehavioral changes in mice.

Methods
Wild-type C57BL/6J female mice were sensitized with nasal house dust mite (HDM) antigen or control PBS for 6 weeks to induce chronic allergic lung inflammation. A series of neurocognitive tests for anxiety and/or depression were performed before and after the intranasal HDM administration. After the behavior tests, tissues were harvested to measure inflammation in the lungs and the brains.

Results
HDM-treated mice exhibited significantly increased immobility times during tail suspension tests and significantly decreased sucrose preference compared with PBS controls, suggesting a more depressed and anhedonia phenotype. Spatial memory impairment was also observed in HDM-treated mice when assessed by the Y-maze novel arm tests. Development of lung inflammation after 6 weeks of HDM administration was confirmed by histology, bronchoalveolar lavage (BAL) cell count and lung cytokine measurements. Serum pro-inflammatory cytokines and Th2-related cytokines levels were elevated in HDM-sensitized mice. In the brain, the chemokine fractalkine was increased in the HDM group. The c-Fos protein, a marker for neuronal activity, Glial Fibrillary Acidic Protein (GFAP) and chymase, a serine protease from mast cells, were increased in the brains from mice in HDM group. Chymase expression in the brain was negatively correlated with the results of sucrose preference rate in individual mice.

Conclusions
6 weeks of intranasal HDM administration in mice to mimic the chronic status of lung inflammation in asthma, caused significant inflammatory histological changes in the lungs, and several behavioral changes consistent with depression and altered spatial memory. Chymase and c-Fos proteins were increased in the brain from HDM-treated mice, suggesting links between lung inflammation and brain mast cell activation, which could be responsible for depression-like behavior.
Mathematical modelling of the CSF system: effects of microstructures and posture on optic nerve subarachnoid space dynamics
Authors: Holmlund Petter , Støverud Karen-Helene , Eklund Anders 
Published: August 2022

Abstract
Background
The pressure difference between the eye and brain in upright postures may be affected by compartmentalization of the optic nerve subarachnoid space (ONSAS). Both pressure and deformation will depend on the microstructures of the ONSAS, and most likely also on ocular glymphatic clearance. Studying these factors could yield important knowledge regarding the translaminar pressure difference, which is suspected to play a role in normal-tension glaucoma.

Methods
A compartment model coupling the ONSAS with the craniospinal CSF system was used to investigate the effects of microstructures on the pressure transfer through the ONSAS during a posture change from supine to upright body postures. ONSAS distensibility was based on MRI measurements. We also included ocular glymphatic flow to investigate how local pressure gradients alter this flow with changes in posture.

Results
A compartmentalization of the ONSAS occurred in the upright posture, with ONSAS porosity (degree of microstructural content) affecting the ONSAS pressure (varying the supine/baseline porosity from 1.0 to 0.75 yielded pressures between − 5.3 and − 2 mmHg). Restricting the minimum computed porosity (occurring in upright postures) to 0.3 prevented compartmentalization, and the ONSAS pressure could equilibrate with subarachnoid space pressure (− 6.5 mmHg) in $$\le$$
≤
1 h. The ocular glymphatics analysis predicted that substantial intraocular-CSF flows could occur without substantial changes in the ONSAS pressure. The flow entering the ONSAS in supine position (both from the intraocular system and from the cranial subarachnoid space) exited the ONSAS through the optic nerve sheath, while in upright postures the flow through the ONSAS was redirected towards the cranial subarachnoid space.

Conclusions
Microstructures affect pressure transmission along the ONSAS, potentially contributing to ONSAS compartmentalization in upright postures. Different pathways for ocular glymphatic flow were predicted for different postures.