bluuebunny/crossref_metadata_2025 huggingface dataset:
Sildenafil, a phosphodiesterase-5 inhibitor, stimulates angiogenesis and bone regeneration in an atrophic non-union model in mice
Authors: Menger Maximilian M. , Bauer David , Bleimehl Michelle , Scheuer Claudia , Braun Benedikt J. , Herath Steven C. , Rollmann Mika F. , Menger Michael D. , Laschke Matthias W. , Histing Tina
Published: September 2023

Non-union formation represents a major complication in trauma and orthopedic surgery. The phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been shown to exert pro-angiogenic and pro-osteogenic effects in vitro and in vivo. Therefore, the aim of the present study was to analyze the impact of sildenafil in an atrophic non-union model in mice. After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. Bone regeneration was analyzed by means of X-ray, biomechanics, photoacoustic and micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses at 2, 5 and 10 weeks after surgery. The animals were treated daily with either 5 mg/kg body weight sildenafil (n = 35) or saline (control; n = 35) per os. Bone formation was markedly improved in defects of sildenafil-treated mice when compared to controls. This was associated with a higher bending stiffness as well as an increased number of CD31-positive microvessels and a higher oxygen saturation within the callus tissue. Moreover, the bone defects of sildenafil-treated animals contained more tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68-positive macrophages and exhibited a higher expression of the pro-angiogenic and pro-osteogenic markers cysteine rich protein (CYR)61 and vascular endothelial growth factor (VEGF) when compared to controls. These findings demonstrate that sildenafil acts as a potent stimulator of angiogenesis and bone regeneration in atrophic non-unions.
Evolutionary trade-off between innate and acquired immune defences in birds
Authors: Minias Piotr , Peng Wei-Xuan V. -H. , Matson Kevin D.
Published: September 2023

Background

The development, maintenance, and use of immune defences are costly. Therefore, animals face trade-offs in terms of resource allocation within their immune system and between their immune system and other physiological processes. To maximize fitness, evolution may favour investment in one immunological defence or subsystem over another in a way that matches a species broader life history strategy. Here, we used phylogenetically-informed comparative analyses to test for relationships between two immunological components. Natural antibodies and complement were used as proxies for the innate branch; structural complexity of the major histocompatibility complex (MHC) region was used for the acquired branch.

Results

We found a negative association between the levels of natural antibodies (i.e., haemagglutination titre) and the total MHC gene copy number across the avian phylogeny, both at the species and family level. The family-level analysis indicated that this association was apparent for both MHC-I and MHC-II, when copy numbers within these two MHC regions were analysed separately. The association remained significant after controlling for basic life history components and for ecological traits commonly linked to pathogen exposure.

Conclusion

Our results provide the first phylogenetically robust evidence for an evolutionary trade-off within the avian immune system, with a more developed acquired immune system (i.e., more complex MHC architecture) in more derived bird lineages (e.g., passerines) being accompanied by an apparent downregulation of the innate immune system.
Evaluation of the efficacy of manual soft tissue therapy and therapeutic exercises in patients with pain and limited mobility TMJ: a randomized control trial (RCT)
Authors: Gębska Magdalena , Dalewski Bartosz , Pałka Łukasz , Kołodziej Łukasz
Published: September 2023

The limited number of randomized controlled trials (RCTs) comparing the efficacy of soft tissue manual therapy and self-therapy interventions prompted the authors to focus on the analgesic and myorelaxant use of massage, post-isometric muscle relaxation (PIR) and therapeutic exercise in TMD patients.

Objectives

To evaluate the effectiveness of soft tissue therapy and therapeutic exercises in female patients with pain, increased masseter muscle tension and limited mandibular mobility.

Material and methods

The study was conducted on a group of 82 women (G1) with the Ib disorder diagnosed in DC/TMD (Ib—myofascial pain with restricted mobility). The control group (G2) consisted of 104 women without diagnosed TMDs (normal reference values for TMJ ROM and masseter muscle sEMG bioelectric activity). Diagnostic procedures were performed in both groups (sEMG of the masseter muscles at baseline and during exercise, measurement of TMJ mobility, assessment of pain intensity—NRS scale). The G1 group was randomly divided into 3 therapeutic groups in which the therapy was carried out for 10 days: therapeutic exercises (TE), manual therapy – massage and therapeutic exercises (MTM_TE), manual therapy – PIR and therapeutic exercises (MTPIR_TE). Each time after therapy, the intensity of pain and TMJ mobility were assessed. Sealed, opaque envelopes were used for randomization. After 5 and 10 days of therapy, bilateral sEMG signals of the masseter muscles were acquired.

Results

Massage, PIR and self-therapy led to a decrease in sEMG at rest as well as in exercise. After day 6 of therapy, the groups obtained a significant difference (p = 0.0001). Each of the proposed forms of therapy showed a minimal clinically significant difference (MID) in the sEMG parameter at the endpoint, with the most considerable difference in the MTM_TE group. The forms of MT used were effective in reducing the patients’ pain intensity; however, a significant difference between therapies occurred after 4 treatments (p = 0.0001). Analyzing the MID between methods, it was observed that self-therapy had an analgesic effect only after 8 treatments, while PIR after 3 and massage after 1 treatment. After day 7, the mean pain score in the MTM_TE group was 0.889 and in the TMPIR_TE group was 3.44 on the NRS scale. In terms of MMO, a significant difference was obtained between monotherapy and each form of TM, i.e. massage (p = 0.0001) and PIR (p = 0.0001). Analyzing mandibular lateral movements, the authors got a significant difference in the proposed MT forms, of which massage treatments exceeded the effectiveness of PIR.

Conclusions

Soft tissue manual therapy and therapeutic exercise are simple and safe interventions that can potentially benefit patients with myogenic TMDs, with massage showing better analgesic effects than PIR.
Familial pancreatic cancer: a case study and review of the psychosocial effects of diagnoses on families
Authors: Lowe Tracy , DeLuca Jane , Abenavoli Ludovico , Boccuto Luigi
Published: September 2023

Background

Familial pancreatic cancer touches families through a genetic susceptibility to developing this neoplasia. Genetic susceptibility is assessed via family history, genetic testing, or both. Individuals with two or more first-degree relatives or three or more relatives of any degree diagnosed with pancreatic cancer are considered at elevated risk. Following a diagnosis of familial pancreatic cancer, patients and families face uncertainty and anxiety about the future. Psychosocial effects of a pancreatic cancer diagnosis on families include fear, concerns about personal health, and how lifestyle may impact the risk of developing pancreatic cancer.

Case presentation

A 66-year-old male was diagnosed with pancreatic ductal adenocarcinoma stage IIB, T3, N1, M0. A genetic referral was made due to a history of multiple cases of pancreatic cancer within the patient’s family. Genetic testing revealed the patient had a pathogenic variant in the ATM gene that is associated with an increased risk for pancreatic cancer development. The patient’s one adult child was offered testing due to the autosomal dominant pattern of inheritance for this variant. The adult child was found to have the same pathogenic variant. She expressed fear for her future and her child’s future health and longevity. Discussing a case study allows us to capture the multi-faceted relationship between the disease, the affected individuals, and their families. Examining the psychosocial stresses and concerns when there is a pancreatic cancer diagnosis in the family is essential to provide holistic care to patients and families.

Conclusions

The psychosocial effects of FPC may be overwhelming for patients and families. Healthcare providers can offer education, support, and referrals to appropriate services to help families cope through stages of evaluation, diagnosis, and treatment of FPC.
Composite dietary antioxidant index was negatively associated with the prevalence of diabetes independent of cardiovascular diseases
Authors: Chen Xiaojie , Lu He , Chen Yingwei , Sang Haiqiang , Tang Yi , Zhao Yifan
Published: September 2023

Aim

The association between composite dietary antioxidant index (CDAI) and diabetes remains unknown. Our study was to investigate the association of CDAI with diabetes.

Methods

A total of 11,956 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES). The CDAI was calculated from the intake of six dietary antioxidants. Multivariable logistic regressions were performed to explore the associations between CDAI and the prevalence of diabetes and glycemic index. Non-linear associations were explored using restricted cubic splines.

Results

In the multivariate logistic regression model, the odds ratio (95% confidence interval) of CDAI associating with obesity was 0.98 (0.97-1.00; p = 0.033). Compared with the lowest quartile, the highest quartile was related to 0.84-fold risk of diabetes (0.71–0.99; p = 0.035). However, CDAI was not independently associated with fasting glucose and hemoglobin A1c.

Conclusion

CDAI was negatively associated with diabetes and the relationship was independent of other traditional risk factors.
A quantum physics layer of epigenetics: a hypothesis deduced from charge transfer and chirality-induced spin selectivity of DNA
Authors: Siebert Reiner , Ammerpohl Ole , Rossini Mirko , Herb Dennis , Rau Sven , Plenio Martin B. , Jelezko Fedor , Ankerhold Joachim
Published: September 2023

Background

Epigenetic mechanisms are informational cellular processes instructing normal and diseased phenotypes. They are associated with DNA but without altering the DNA sequence. Whereas chemical processes like DNA methylation or histone modifications are well-accepted epigenetic mechanisms, we herein propose the existence of an additional quantum physics layer of epigenetics.

Results

We base our hypothesis on theoretical and experimental studies showing quantum phenomena to be active in double-stranded DNA, even under ambient conditions. These phenomena include coherent charge transfer along overlapping pi-orbitals of DNA bases and chirality-induced spin selectivity. Charge transfer via quantum tunneling mediated by overlapping orbitals results in charge delocalization along several neighboring bases, which can even be extended by classical (non-quantum) electron hopping. Such charge transfer is interrupted by flipping base(s) out of the double-strand e.g., by DNA modifying enzymes. Charge delocalization can directly alter DNA recognition by proteins or indirectly by DNA structural changes e.g., kinking. Regarding sequence dependency, charge localization, shown to favor guanines, could influence or even direct epigenetic changes, e.g., modification of cytosines in CpG dinucleotides. Chirality-induced spin selectivity filters electrons for their spin along DNA and, thus, is not only an indicator for quantum coherence but can potentially affect DNA binding properties.

Conclusions

Quantum effects in DNA are prone to triggering and manipulation by external means. By the hypothesis put forward here, we would like to foster research on “Quantum Epigenetics” at the interface of medicine, biology, biochemistry, and physics to investigate the potential epigenetic impact of quantum physical principles on (human) life.
Evaluation of the application of sequence data to the identification of outbreaks of disease using anomaly detection methods
Authors: Díaz-Cao José Manuel , Liu Xin , Kim Jeonghoon , Clavijo Maria Jose , Martínez-López Beatriz
Published: September 2023

Anomaly detection methods have a great potential to assist the detection of diseases in animal production systems. We used sequence data of Porcine Reproductive and Respiratory Syndrome (PRRS) to define the emergence of new strains at the farm level. We evaluated the performance of 24 anomaly detection methods based on machine learning, regression, time series techniques and control charts to identify outbreaks in time series of new strains and compared the best methods using different time series: PCR positives, PCR requests and laboratory requests. We introduced synthetic outbreaks of different size and calculated the probability of detection of outbreaks (POD), sensitivity (Se), probability of detection of outbreaks in the first week of appearance (POD1w) and background alarm rate (BAR). The use of time series of new strains from sequence data outperformed the other types of data but POD, Se, POD1w were only high when outbreaks were large. The methods based on Long Short-Term Memory (LSTM) and Bayesian approaches presented the best performance. Using anomaly detection methods with sequence data may help to identify the emergency of cases in multiple farms, but more work is required to improve the detection with time series of high variability. Our results suggest a promising application of sequence data for early detection of diseases at a production system level. This may provide a simple way to extract additional value from routine laboratory analysis. Next steps should include validation of this approach in different settings and with different diseases.
Heterogeneity of pathological prion protein accumulation in the brain of moose (Alces alces) from Norway, Sweden and Finland with chronic wasting disease
Authors: Sola Diego , Tran Linh , Våge Jørn , Madslien Knut , Vuong Tram T. , Korpenfelt Sirkka Liisa , Ågren Erik O. , Averhed Gustav , Nöremark Maria , Sörén Kaisa , Isaksson Mats , Acín Cristina , Badiola Juan José , Gavier-Widén Dolores , Benestad Sylvie L.
Published: September 2023

Prion diseases are a group of neurodegenerative, transmissible, and fatal disorders that affect several animal species. They are characterized by the conformational conversion of the cellular prion protein (PrPC) into the pathological prion protein (PrPSc). In 2016, chronic wasting disease (CWD) gained great importance at European level due to the first disease detection in a wild reindeer (Rangifer tarandus) in Norway. The subsequent intensive CWD surveillance launched in cervids resulted in the detection of CWD in moose (Alces alces), with 11 cases in Norway, 3 in Finland and 4 in Sweden. These moose cases differ considerably from CWD cases in North American and reindeer in Norway, as PrPSc was detectable in the brain but not in lymphoid tissues. These facts suggest the occurrence of a new type of CWD. Here, we show some immunohistochemical features that are clearly different from CWD cases in North American and Norwegian reindeer. Further, the different types of PrPSc deposits found among moose demonstrate strong variations between the cases, supporting the postulation that these cases could carry multiple strains of CWD.
Fluid shear stress induces a shift from glycolytic to amino acid pathway in human trophoblasts
Authors: Brugger Beatrice Anna , Neuper Lena , Guettler Jacqueline , Forstner Désirée , Wernitznig Stefan , Kummer Daniel , Lyssy Freya , Feichtinger Julia , Krappinger Julian , El-Heliebi Amin , Bonstingl Lilli , Moser Gerit , Rodriguez-Blanco Giovanny , Bachkönig Olaf A. , Gottschalk Benjamin , Gruber Michael , Nonn Olivia , Herse Florian , Verlohren Stefan , Frank Hans-Georg , Barapatre Nirav , Kampfer Cornelia , Fluhr Herbert , Desoye Gernot , Gauster Martin
Published: September 2023

Background

The human placenta, a tissue with a lifespan limited to the period of pregnancy, is exposed to varying shear rates by maternal blood perfusion depending on the stage of development. In this study, we aimed to investigate the effects of fluidic shear stress on the human trophoblast transcriptome and metabolism.

Results

Based on a trophoblast cell line cultured in a fluidic flow system, changes caused by shear stress were analyzed and compared to static conditions. RNA sequencing and bioinformatics analysis revealed an altered transcriptome and enriched gene ontology terms associated with amino acid and mitochondrial metabolism. A decreased GLUT1 expression and reduced glucose uptake, together with downregulated expression of key glycolytic rate-limiting enzymes, hexokinase 2 and phosphofructokinase 1 was observed. Altered mitochondrial ATP levels and mass spectrometry data, suggested a shift in energy production from glycolysis towards mitochondrial oxidative phosphorylation. This shift in energy production could be supported by increased expression of glutamic-oxaloacetic transaminase variants in response to shear stress as well as under low glucose availability or after silencing of GLUT1. The shift towards amino acid metabolic pathways could be supported by significantly altered amino acid levels, like glutamic acid, cysteine and serine. Downregulation of GLUT1 and glycolytic rate-limiting enzymes, with concomitant upregulation of glutamic-oxaloacetic transaminase 2 was confirmed in first trimester placental explants cultured under fluidic flow. In contrast, high fluid shear stress decreased glutamic-oxaloacetic transaminase 2 expression in term placental explants when compared to low flow rates. Placental tissue from pregnancies with intrauterine growth restriction are exposed to high shear rates and showed also decreased glutamic-oxaloacetic transaminase 2, while GLUT1 was unchanged and glycolytic rate-limiting enzymes showed a trend to be upregulated. The results were generated by using qPCR, immunoblots, quantification of immunofluorescent pictures, padlock probe hybridization, mass spectrometry and FRET-based measurement.

Conclusion

Our study suggests that onset of uteroplacental blood flow is accompanied by a shift from a predominant glycolytic- to an alternative amino acid converting metabolism in the villous trophoblast. Rheological changes with excessive fluidic shear stress at the placental surface, may disrupt this alternative amino acid pathway in the syncytiotrophoblast and could contribute to intrauterine growth restriction.
SARS-CoV-2 risk in household contacts of healthcare workers: a prospective cohort study
Authors: Kohler Philipp , Dörr Tamara , Friedl Andrée , Stocker Reto , Vuichard Danielle , Kuster Stefan P. , Kahlert Christian R. ,   the SURPRISE Study Group, Besold Ulrike , Betschon Elsbeth , Brucher Angela , Cusini Alexia , Friedl Andrée , Goppel Stephan , Grässli Fabian , Kahlert Christian R. , Keller Joelle , Kessler Simone , Kohler Philipp , Kuster Stefan P. , Leal Onicio , Lemmenmeier Eva , McGeer Allison , Kleeb Dorette Meier , Möller Elisabeth , Möller J. Carsten , Müller Maja F. , Musa Vaxhid , Ortner Manuela , Rieder Philip , Risch Lorenz , Ruetti Markus , Schlegel Matthias , Schmid Hans-Ruedi , Stocker Reto , Vernazza Pietro , von Kietzell Matthias , Vuichard-Gysin Danielle , Wiggli Benedikt
Published: September 2023

Background

Few studies have assessed whether the increased SARS-CoV-2 risk of healthcare workers (HCW) is carried on to their household contacts. Within a prospective HCW cohort, we assessed the SARS-CoV-2 risk of household contacts of HCW depending on the HCWs cumulative exposure to COVID-19 patients and identified factors influencing this association.

Methods

HCW aged ≥ 16 years from nine Swiss healthcare networks participated. HCW without any household contacts were excluded. For HCW, cumulative patient exposure (number of COVID-19 patient contacts times average contact duration during a 12-month follow-up) was calculated. During follow-up, HCW reported SARS-CoV-2 nasopharyngeal swab results and positive swab results of their household contacts. We used multivariable logistic regression to identify variables associated with SARS-CoV-2 household positivity.

Results

Of 2406 HCW, 466 (19%) reported ≥ 1 SARS-CoV-2 positive household. In multivariable analysis, patient exposure of HCW (adjusted OR [aOR] 1.08 per category, 95% CI 1.04–1.12), household size (aOR 1.53 per household member, 95% CI 1.35–1.73) and having children (aOR 0.70, 95% CI 0.53–0.94) remained associated with household positivity. Vaccinated HCW had a lower risk (aOR 0.54, 95% CI 0.38–0.77) of reporting a positive contact, as were those using respirator masks in contact with COVID-19 patients (aOR 0.65, 95% CI 0.49–0.86). Among vaccinated HCW, delayed first vaccination was associated with increased household SARS-CoV-2 positivity (aOR 1.14 per month, 95% CI 1.08–1.21).

Conclusions

SARS-CoV-2 positivity in household contacts of HCW increases with higher cumulative COVID-19 patient exposure of HCWs. Measures reducing the SARS-CoV-2 risk in HCW might indirectly reduce the infection risk of their households.
Cash for assets during acute food insecurity: an observational study in South Sudan
Authors: Doocy Shannon , Lyles Emily , Morjan Robert Kenyi , Pfieffer-Mundt Kayla , Robinson Courtland , Savage Kevin
Published: September 2023

Background

Cash-based assistance in humanitarian contexts has grown substantially in recent years, yet little is empirically known about differential impacts of cash for diverse beneficiaries, which could better inform assistance targeting. In the context of increasing food insecurity and extreme levels of famine in South Sudan despite significant scale-up of humanitarian assistance, this analysis examined food security and household economy outcomes to better understand the impact of cash assistance and characteristics associated with worsened household food security and coping strategies.

Methods

In 2019–2021, a prospective cohort study was conducted leveraging a program providing cash for work in community gardens. 1213 households receiving cash prior to the start of the study (Cohort A/B), 582 non-intervention households (Control), and 300 households that received cash after the start of the study (Cohort C) completed 2 interviews spaced one year apart to measure household food insecurity and coping mechanism adoption.

Results

There were no significant differences in change over time in household hunger score (p = 0.074), livelihoods coping strategy index score (p = 0.104), or meal frequency (p = 0.113) between program participants and the comparison group. The comparison group had a significantly larger increase in dietary diversity over time (0.6 vs. 0.2 in Cohort A/B, p = 0.005); however, at endline there were no significant differences in dietary diversity between program participants and the non-intervention group (4.3 in both groups). There were few factors associated with increased likelihood of worsened food security and coping outcomes, the most noticeable being recent investment livestock, which was associated with 1.5 times greater odds of worsened hunger and 1.63 times greater odds of worsened coping strategy adoption.

Conclusion

Cash transfers did not appear to have lasting benefits on food security and livelihoods coping strategy use. Larger transfer sizes may need to be considered in future programming to achieve more substantial improvements in household food security; however, maintaining rather than improving household food security may be sufficient in worsening food crises contexts.
Development of isotope dilution-liquid chromatography tandem mass spectrometry for the accurate determination of vitamin K1 in spinach and kimchi cabbage
Authors: Lee Hyeyoung , Lee Joonhee , Lee Honghee , Kim Byungjoo
Published: September 2023

In the human body, vitamin K1 is important for bone and cardiovascular health and blood coagulation. To assess the correlation between vitamin K1 intake and health outcomes, the accurate determination of the amounts of vitamin K1 in green leafy vegetables, which are its major source in the diet, is needed. In this study, an accurate method for quantifying naturally occurring trans- and cis-vitamin K1 in spinach and kimchi cabbage was developed on the basis of isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC/MS/MS). A C30 column was employed for proper separation of trans- and cis-vitamin K1 isomers, and vitamin K1-d7 was used as an internal standard. The developed method was validated by measuring gravimetrically fortified samples, and its performance parameters were evaluated. The measured results agreed with the gravimetric results with a difference of less than 3%. The repeatability and reproducibility of the vitamin K1 analysis were less than 2% relative standard deviation, indicating that the method had a higher-order metrological quality as a reference method.
Supporting families and caregivers of children with disabilities through a parent peer mentor (PPM): experiences from a patient-oriented research network
Authors: Yamaguchi Sakiko , Costello Carrie , Lalonde Corinne , McCarry Sharon , Majnemer Annette , Shikako Keiko
Published: September 2023

Background

The CHILD-BRIGHT Network created a parent peer mentor (PPM) role to support other parents who were engaging as partners in the different research projects and activities of the network. We aim to describe how a PPM functioned to support parent-partners of children with disabilities in research projects within the Network.

Methods

In this case study, the PPM approached 50 parent-partners and scheduled a 1-on-1 initial telephone call to offer support for any issues arising. When consent was provided, the PPM recorded interactions with network parent-partners in a communication report in an Excel form. Also, verbatim transcription from one in-depth interview with the PPM was included for data analysis using qualitative description. The Guidance for Reporting Involvement of Patients and the Public (GRIPP2-SF) was used to report on involvement of patient-partners.

Results

A total of 55 interactions between 25 parent-partners and the PPM were documented between May 2018 and June 2021. The PPM’s support and liaison role contributed to adaptation of meeting schedules for parent-partners, amendment of the compensation guidelines, and ensuring that internal surveys and the newsletter were more accessible and engaging. The PPM also facilitated community-building by keeping parent-partners connected with researchers in the Network. Families and caregivers in the Network were comfortable sharing their experiences and emotions with the PPM who was also a parent herself, allowing researchers and the Network to learn more about parents’ experiences in partnering with them and how to improve engagement.

Conclusions

We highlight the important complementary role that a PPM can play in enhancing patient engagement in research by better understanding the experiences and needs of parent-partners.
Putting the “learning” in “pre-learning”: effects of a self-directed study hall on skill acquisition in a simulation-based central line insertion course
Authors: Diederich Emily , Lineberry Matthew , Schott Vanessa , Broski Julie , Alsayer Ahmed , Eckels Krista A. , Murray Megan J. , Huynh William , Thomas Laura A.
Published: September 2023

Background

Opportunities to practice procedural skills in the clinical learning environment are decreasing, and faculty time to coach skills is limited, even in simulation-based training. Self-directed learning with hands-on practice early in a procedural skill course might help maximize the benefit of later faculty coaching and clinical experience. However, it may also lead to well-learned errors if learners lack critical guidance. The present study sought to investigate the effects of a hands-on, self-directed “study hall” for central line insertion among first-year residents.

Methods

Learner cohorts before vs. after introduction of the study hall (n = 49) were compared on their pre- and post-test performance of key procedural behaviors that were comparable across cohorts, with all learners receiving traditional instructor-led training between tests.

Results

Study hall participants spent a median of 116 min in hands-on practice (range 57–175). They scored higher at pre-test (44% vs. 27%,p = .00; Cohen’sd = 0.95) and at post-test (80% vs. 72%,p = .02; Cohen’sd = 0.69). A dose–response relationship was found, such that 2 h of study hall were roughly equivalent to the performance improvement seen with four clinical observations or supervised insertions of central lines.

Conclusions

Self-directed, hands-on “study hall” supported improved procedural skill learning in the context of limited faculty availability. Potential additional benefits make the approach worth further experimentation and evaluation.
A disease-specific iPS cell resource for studying rare and intractable diseases
Authors: Saito Megumu K. , Osawa Mitsujiro , Tsuchida Nao , Shiraishi Kotaro , Niwa Akira , Woltjen Knut , Asaka Isao , Ogata Katsuhisa , Ito Suminobu , Kobayashi Shuzo , Yamanaka Shinya
Published: September 2023

Background

Disease-specific induced pluripotent stem cells (iPSCs) are useful tools for pathological analysis and diagnosis of rare diseases. Given the limited available resources, banking such disease-derived iPSCs and promoting their widespread use would be a promising approach for untangling the mysteries of rare diseases. Herein, we comprehensively established iPSCs from patients with designated intractable diseases in Japan and evaluated their properties to enrich rare disease iPSC resources.

Methods

Patients with designated intractable diseases were recruited for the study and blood samples were collected after written informed consent was obtained from the patients or their guardians. From the obtained samples, iPSCs were established using the episomal method. The established iPSCs were deposited in a cell bank.

Results

We established 1,532 iPSC clones from 259 patients with 139 designated intractable diseases. The efficiency of iPSC establishment did not vary based on age and sex. Most iPSC clones originated from non-T and non-B hematopoietic cells. All iPSC clones expressed key transcription factors, OCT3/4 (range 0.27–1.51; mean 0.79) and NANOG (range 0.15–3.03; mean 1.00), relative to the reference 201B7 iPSC clone.

Conclusions

These newly established iPSCs are readily available to the researchers and can prove to be a useful resource for research on rare intractable diseases.
Osteoporosis-related fractures in men and women with established and early rheumatoid arthritis: predictors and risk compared with the general population
Authors: Theander Lisa , Jacobsson Lennart T.H. , Turesson Carl
Published: September 2023

Objectives

To study the risk of osteoporosis-related fractures in a community-based sample of men and women with rheumatoid arthritis (RA) overall, as well as early (< 1 year of disease duration, follow-up time maximum 10 years) and established (RA diagnosis since ≥ 5 years on July 1, 1997) RA, compared with the general population. To study potential risk factors for fractures in patients with RA from baseline questionnaire data.

Methods

A community-based cohort of patients with RA (n = 1928) was studied and compared to matched general population controls. Information on osteoporosis-related fractures (hip, proximal upper arm, distal forearm and vertebral fractures) during the period July 1, 1997 to December 31, 2017 was obtained by linkage to the Swedish National Inpatient Register and the Cause of Death Register. The incidence of fractures was estimated in patients and controls. Cox regression models were used to assess the relation between RA and the risk of fractures and to assess potential predictors of fractures in RA patients. Analyses were stratified by sex, and performed in all patients with RA, and in subsets with early and established RA.

Results

The overall incidence of osteoporosis-related fractures in the RA cohort was 10.6 per 1000 person-years (95% CI 9.31; 12.0). There was an increased risk of fractures overall in both men (hazard ratio (HR) 1.55, 95% CI 1.03; 2.34) and women (HR 1.52; 95% CI 1.27; 1.83) with RA compared to controls, with significantly increased risk also in the hip. No increased risk of osteoporosis-related fractures overall was seen in patients with early RA (HR 1.01, 95% CI 0.69; 1.49). Higher age, longer duration of RA, higher HAQ scores and higher scores in the visual analogue scale for global health were predictors of fractures.

Conclusion

Both men and women with RA were at increased risk of osteoporosis-related fractures. Patients with early RA did not have significantly increased risk during the first 10 years of disease in this study.
Infertility diagnosis and management
Authors: Mansour Hend Abd El-halim
Published: September 2023

Background

One of the most stressful problems for married couples is infertility, which is a widespread health issue. It has been defined as a profound life-changing problem that comes with severe psychological stress despite the fact that it is not fatal. The rate of infertility among couples is gradually rising due to postponing childbearing, which is brought on by several social and economic causes.

Main body

Depending on the cause, the length of the couple’s struggle, and the ages of the partners, infertility can be treated medically, surgically, or with modern reproductive assistance (in vitro fertilisation, intrauterine insemination, intracytoplasmic sperm injection, and nanotechnology). Fertility issues can be a stressful circumstance in a person’s life with serious psychological repercussions. Hypogonadotropic hypogonadism, hyperprolactinemia, ciliary disorders, cystic fibrosis, infections, systemic diseases, and diseases connected to lifestyle are the factors that impair fertility in both sexes. Female infertility may be caused by premature ovarian insufficiency, polycystic ovary syndrome, endometriosis, uterine fibroids, and pelvic inflammatory disease. Testicular and post-testicular deficits can cause male infertility. Other potential contributing factors include consanguinity, endocrine disrupting substances, and the observed semen reduction throughout time.

Conclusion

One in eight females between the ages of 15 and 49 receives assistance with conception. Although success rates vary by age and diagnosis, many couples receiving treatment for infertility can achieve their fertility objectives with the help of a precise diagnosis, efficient therapy, and shared decision-making. The term “assisted reproductive technology” can facilitate egg fertilisation and aid implantation of the fertilised egg in the uterine lining.
Constraints and insights into the tectonics of the Bayan Obo deposit from the shallow velocity structure
Authors: Zhu Dengda , Wang Jian , He Lanfang , Chen Weiying , Yang Kuifeng , Li Xiaochun , Xue Guoqiang , Fan Hongrui , Xu Ya , Zhang Lili , Huang Song , Wang Yibo , Zhang Jien , Tian Xiaobo , Zhao Liang , Liu Yun , Liu Zhanquan , Zhao Yonggang , Yang Zhanfeng , Li Xianhua
Published: September 2023

The Bayan Obo deposit in Inner Mongolia is a crucial source of rare earth elements-niobium-iron, with significant economic importance for China. The ore-bearing dolomite is believed to have originated from mantle-derived magma, indicating high prospectivity in the deeper sections. However, the deep distribution of the ore-bearing dolomite remains poorly understood. Here, we develop a 3D S-wave velocity ([Formula: see text]) structure down to 2.5 km depth beneath the Bayan Obo using ambient noise tomography techniques, which used 25 days of continuous waveform data recorded by 312 short-period seismometers. Combined with previous geological, geochemical, and geophysical studies, our results reveal the possible 3D spatial distribution of the ore-bearing dolomite beneath the Bayan Obo. The results indicate that the [Formula: see text] structures beneath the main, east, and west pits change from relatively high-velocity (high-V) zones (with [Formula: see text] of approximately 2.8–3.2 km/s) at shallow depths (depth to approximately 1.5–1.8 km) to significant low-velocity (low-V) zones (with [Formula: see text] < 2.6 km/s) at deeper depths (depth below approximately 1.8 km). We suggest that the content of ore-bearing dolomite may decrease significantly at deeper depths (depth below approximately 1.8 km) beneath these pits, which possibly indicates a diminished prospecting potential there. Our results also indicate a significant high-V zone (with [Formula: see text] > 3.4 km/s) at depths of approximately 1–2.5 km between the main and west pits. Its lithology remains unclear and is proposed to be a key scientific issue in the future to improve our understanding of the ore-controlling structure associated with the tectonic events in the Bayan Obo deposit.
Digital rock advances from a material point method approach for simulation of frame moduli and a sedimentary petrology-inspired method for creation of synthetic samples through simulation of deposition and diagenesis
Authors: Lander Robert H. , Cook Jennie E. , Guilkey James , Kerimov Abdulla , Bonnell Linda M. , Goodwin Laurel B.
Published: September 2023

We compare hydromechanical simulation results that use two alternative sources of 3D digital rock input: micro-CT analysis and “synthetic rocks” created by using a newly developed process simulation methodology that more rigorously reflects knowledge from sedimentary petrology compared with previous efforts. We evaluate the performance of these alternative representations using St. Peter Sandstone samples where “dry” static bulk modulus ( K) and shear modulus ( G) are simulated using a new extension of the material point method that resolves contacts using high-resolution surface meshes and considers three alternative contact modeling approaches: “purely frictional,” “fully bonded,” and “cohesive zones.” We evaluate the model performance on two samples from the data set with multiple static moduli measurements (sample 1_2: porosity 24.6 vol%, K 10.2–14.7 GPa, and G 11.6–14.0 GPa; sample 11_2: porosity 12.4 vol%, K 13.5–24.6 GPa, and G 12.8–17.9 GPa). Purely frictional results underpredict measured modulus values, whereas fully bonded results overpredict them. Measured values are most closely approximated by results with cohesive zones that consider sets of discrete spring-like features at contacts. In contrast, shear modulus results from finite-element model simulations on structured grids tend to be significantly greater than measured values, particularly for samples with <18 vol% porosity. Permeability values from digital rock-physics simulations for the studied samples are within factors of 2–5 of conventional core analysis measurements (2860 and 58 mD for samples 1_2 and 11_2, respectively). We determine that the process modeling approach (1) accurately reproduces the measured rock microstructure parameters from thin-section analysis, (2) leads to simulation results for dry static moduli and permeability with accuracy comparable to simulations that use micro-CT samples, and (3) provides a rigorous basis for predicting diagenetically induced variations in hydromechanical properties over the range from unconsolidated sand to indurated rock.
Pediatric Renal Transplant With Dilated Cardiomyopathy: A Stepwise Hemodynamic Management—A Case Report
Authors: Garg Kashish , Kayina Choro Athiphro , Kajal Kamal , Gourav Krishna Prasad , Aditya Ashish , Sethi Sameer , Kenwar Deepesh B.
Published: September 2023

Here we have described the anesthetic management of a 10-year-old patient having uremia-induced dilated cardiomyopathy for a living-related adult to pediatric renal transplant. Maintaining optimal hemodynamics, especially during the reperfusion phase, is crucial for maintaining graft perfusion. However, dilated cardiomyopathy limits indiscriminate fluid administration as it may cause congestive heart failure and pulmonary edema. We have described the fluid therapy algorithm based on the plethysmography variability index and velocity time integral at the left ventricular outflow tract, which was able to limit excessive fluid administration and maintain adequate perfusion pressures.
The Swedish Kinship Universe: A Demographic Account of the Number of Children, Parents, Siblings, Grandchildren, Grandparents, Aunts/Uncles, Nieces/Nephews, and Cousins Using National Population Registers
Authors: Kolk Martin , Andersson Linus , Pettersson Emma , Drefahl Sven
Published: September 2023

Given that surprisingly little is known about the demography of human kinship, we provide a demographic account of the kinship networks of individuals in Sweden in 2017 across sex and cohort between ages 0 and 102. We used administrative register data of the full population of Sweden to provide the first kinship enumeration for a complete population based on empirical data. We created ego-focused kinship networks of children, parents, siblings, grandchildren, grandparents, aunts and uncles, nieces and nephews, and cousins. We show the average number of kin of different types, the distribution of the number of kin, and changes in dispersion over time. A large share of all kin of an individual are horizontal kin, such as cousins. We observe the highest number of kin—on average, roughly 20—around age 35. We show differences between matrilineal and patrilineal kin and differences in the kinship structure arising from fertility with more than one childbearing partner, such as half-siblings. The results demonstrate substantial variability in kinship within a population. We discuss our findings in the context of other methods to estimate kinship.
Wnt9 directs zebrafish heart tube assembly via a combination of canonical and non-canonical pathway signaling
Authors: Paolini Alessio , Sharipova Dinara , Lange Tim , Abdelilah-Seyfried Salim
Published: September 2023

During zebrafish heart formation, cardiac progenitor cells converge at the embryonic midline where they form the cardiac cone. Subsequently, this structure transforms into a heart tube. Little is known about the molecular mechanisms that control these morphogenetic processes. Here, we use light-sheet microscopy and combine genetic, molecular biological and pharmacological tools to show that the paralogous genes wnt9a/b are required for the assembly of the nascent heart tube. In wnt9a/b double mutants, cardiomyocyte progenitor cells are delayed in their convergence towards the embryonic midline, the formation of the heart cone is impaired and the transformation into an elongated heart tube fails. The same cardiac phenotype occurs when both canonical and non-canonical Wnt signaling pathways are simultaneously blocked by pharmacological inhibition. This demonstrates that Wnt9a/b and canonical and non-canonical Wnt signaling regulate the migration of cardiomyocyte progenitor cells and control the formation of the cardiac tube. This can be partly attributed to their regulation of the timing of cardiac progenitor cell differentiation. Our study demonstrates how these morphogens activate a combination of downstream pathways to direct cardiac morphogenesis.
An acytokinetic cell division creates PIP2-enriched membrane asymmetries leading to slit diaphragm assembly in Drosophila nephrocytes
Authors: Carrasco-Rando Marta , Culi Joaquim , Campuzano Sonsoles , Ruiz-Gómez Mar
Published: September 2023

Vertebrate podocytes and Drosophila nephrocytes display slit diaphragms, specialised cell junctions that are essential for the execution of the basic excretory function of ultrafiltration. To elucidate the mechanisms of slit diaphragm assembly we have studied their formation in Drosophila embryonic garland nephrocytes. These cells of mesenchymal origin lack overt apical-basal polarity. We find that their initial membrane symmetry is broken by an acytokinetic cell division that generates PIP2-enriched domains at their equator. The PIP2-enriched equatorial cortex becomes a favourable domain for hosting slit diaphragm proteins and the assembly of the first slit diaphragms. Indeed, when this division is either prevented or forced to complete cytokinesis, the formation of diaphragms is delayed to larval stages. Furthermore, although apical polarity determinants also accumulate at the equatorial cortex, they do not appear to participate in the recruitment of slit diaphragm proteins. The mechanisms we describe allow the acquisition of functional nephrocytes in embryos, which may confer on them a biological advantage similar to the formation of the first vertebrate kidney, the pronephros.
Correlation analysis and clinical significance of Musculoskeletal Ultrasound semi-quantitative grading with bone salt metabolism, Rheumatoid factor and Erythrocyte Sedimentation rate in patients with Rheumatoid Arthritis
Authors: Song Pei-ze , Wu Nan , Huo Cong , Wang Xiao-ming
Published: September 2023

Objective: To determine the correlation and clinical significance of musculoskeletal ultrasound semi-quantitative grading with bone salt metabolism, rheumatoid factor and erythrocyte sedimentation rate (ESR) in patients with rheumatoid arthritis.

Methods: This is a clinical comparative study. A total of 240 patients with rheumatoid arthritis admitted to Baoding NO.1 Central Hospital were selected according to the DAS28 score of rheumatoid arthritis, and were divided into four groups, with 60 cases in each group from May 2020 to May 2022. The differences and correlation of musculoskeletal ultrasound semi-quantitative grading, bone metabolism indicators, erythrocyte sedimentation rate and rheumatoid factor among the four groups were statistically analyzed.

Results: The scores of bone erosion, synovial hyperplasia, joint effusion and intrasynovial blood flow in Group-H were significantly higher than those in Group-R, L and M, with statistically significant differences(p=0.00). The procollagen Type-1 N-terminal propeptide(P1NP), bone-specific alkaline phosphatase(BALP) and osteoprotegerin(OPG) in Group-H were significantly lower than those in Group-R, L and M, with statistically significant differences(p=0.00); The tartrate-resistant acid phosphatase(TRAC) in Group-H was significantly higher than that in Group-R, L and M, with a statistically significant difference(p=0.00). The levels of RF and ESR in Group-H were significantly higher than those in Group-R, L and M, with statistically significant differences(p=0.00).

Conclusion: Musculoskeletal ultrasound semi-quantitative grading is correlated with the level of bone salt metabolism, rheumatoid factor and ESR in patients with rheumatoid arthritis. It can be combined with laboratory examination to objectively judge the severity of the course of rheumatoid arthritis.

doi: https://doi.org/10.12669/pjms.39.6.7144

How to cite this: Song P, Wu N, Huo C, Wang X. Correlation analysis and clinical significance of Musculoskeletal Ultrasound semi-quantitative grading with bone salt metabolism, Rheumatoid factor and Erythrocyte Sedimentation rate in patients with Rheumatoid Arthritis. Pak J Med Sci. 2023;39(6):---------. doi: https://doi.org/10.12669/pjms.39.6.7144

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.