bluuebunny/crossref_metadata_2025 huggingface dataset:
The optimal period for oocyte retrieval after the administration of recombinant human chorionic gonadotropin in in vitro fertilization
Authors: Al Rahwanji Mhd Jawad , Abouras Homam , Shammout Mhd Said , Altalla Ray , Al Sakaan Reem , Alhalabi Nawras , Alhalabi Marwan
Published: March 2022

Background

Our objective was to investigate the existence of an optimal period for oocyte retrieval in regards to the clinical pregnancy occurrence after the administration of recombinant human chorionic gonadotropin (rhCG) (Ovitrelle®).

Methods

We studied the digital records of 3362 middle eastern couples who underwent in vitro fertilization (IVF) treatment between 2019 and 2021.

Results

Through statistical testing, we found that there is a significant positive correlation between the oocyte retrieval period and the clinical pregnancy occurrence up to the 37th hour, where retrieval at the 37th hour was found to provide the most optimal outcome, especially in the case of gonadotropin-releasing hormone agonist (GnRHa) long protocol.

Conclusions

This cohort study recommends retrieval at hour 37 after ovulation triggering under the described conditions.
Association between weight loss, change in physical activity, and change in quality of life following a corporately sponsored, online weight loss program
Authors: Höchsmann Christoph , Dorling James L. , Martin Corby K. , Earnest Conrad P. , Church Timothy S.
Published: March 2022

Background

The physiological benefits associated with corporately sponsored weight loss programs are increasingly well documented. However, less is known about how these programs affect employees’ quality of life (QoL). The purpose of the present analysis was to examine the association between weight loss, change in physical activity, and change in QoL following a corporately sponsored, online weight loss program.

Methods

We examined the relationship between weight loss, self-reported change in physical activity, and change in several QoL indices in 26,658 participants (79% women) after the initial 10 weeks of the online weight loss program. The trend in changes in each QoL index with increasing weight loss and change in physical activity was examined using logistic regression analysis.

Results

We observed greater improvements in each QoL index with increasing weight loss (p-for-trend, < 0.001) as well as with progressive increases in physical activity (p-for-trend, < 0.001). The combination of increasing weight loss and increases in physical activity were associated with the greatest improvements in each QoL index (additive effect). The percentage of employees reporting improvements in QoL (“improved” or “very much improved”) was 64% for energy, 63% for mood, 33% for sleep, 65% for self-confidence, 68% for indigestion, and 39% for musculoskeletal pain.

Conclusions

Among people, who engage with a commercial weight loss program, greater weight loss during the program was associated with greater improvements in QoL, and increases in physical activity further enhanced the QoL-related benefits.
Three-dimensional reconstruction and virtual reposition of fragments compared to two dimensional measurements of midshaft clavicle fracture shortening
Authors: Öztürk Mehmet , Paulin Emilie , Charbonnier Caecilia , Dupuis-Lozeron Elise , Holzer Nicolas
Published: March 2022

Background

Midshaft clavicle fracture shortening measurement is a reported key element for indication to surgical management and reporting of clinical trials. Determination of pre-fracture clavicle length for shortening measurement remains an unresolved issue. The purpose of the study was to assess accuracy of a novel technique of three-dimensional reconstruction and virtual reposition of bone fragments (3D-VR) for determination of pre-fracture clavicle length and measurement of shortening.

Methods

Accuracy of 3D-VR measurements was assessed using 5 synthetic bone clavicle fracture models. Measurements were compared between caliper and 3D-VR technique measurements. Correlation between 3D-VR and 2D measurements on standard radiographs was assessed on a cohort of 20 midshaft fractures. Four different methods for 2D measurements were assessed.

Results

Mean difference between caliper measurements and 3D-VR was 0.74 mm (95CI = − 2.51;3.98) (p = 0.56) on synthetic fracture models. Mean differences between 3D-VR and standard radiograph shortening measurement methods were 11.95 mm (95CI = 7.44;16.46) for method 1 (Jeray et al.) and 9.28 mm (95CI = 4.77;13.79) for method 2 (Smekal et al.) (p < 0.05). Differences were − 1.02 mm (95CI = − 5.53;3.48) for method 3 (Silva et al.) and − 2.04 mm (95CI = − 6.55;2.47) for method 4 (own method). Interobserver correlation ranged between 0.85 and 0.99. A false positive threshold of 20 mm was measured by the two observers in 25% of the case according to method of method 1, 30–35% with method 2, 15% with method 3 et al. and 5–10% with the method 4.

Conclusion

3D VR is accurate in measuring midshaft clavicle fracture length and shortening. Two dimensional measurements may be used for approximation of clavicular shortening.
Congenital adrenal hyperplasia with homozygous and heterozygous mutations: a rare family case report
Authors: Cheng Tiantian , Liu Jing , Sun Wenwen , Song Guangyao , Ma Huijuan
Published: March 2022

Background

Congenital adrenal hyperplasia (CAH), characterized by defective adrenal steroidogenesis, is transmitted in an autosomal recessive manner. Mutations in the steroid 21-hydroxylase geneCYP21A2causing steroid 21-hydroxylase deficiency account for most cases of CAH. The c.145l-1452delGGinsC gene mutation is rare, and only one case has been reported, but the form of gene mutation is different from this case, resulting in different clinical phenotype. The most common pathogenic genotype of CAH is a homozygous or compound heterozygous mutation, but CAH patients homozygous for the p.I173N mutation and heterozygous for the c.1451-1452delGGinsC mutation have not been reported previously. We report herein a familial case of CAH, in which both siblings carry the rare homozygous p.I173N mutation and heterozygous c.1451-1452delGGinsC mutation.

Case presentation

The proband showed amenorrhea, infertility, polycystic ovaries, and increased levels of androgen, rather than the typical clinical manifestations of CAH such as an adrenal crisis or masculine vulva, so was misdiagnosed with polycystic ovary syndrome for many years. Following a correct diagnosis of CAH, she was given glucocorticoid treatment, her menstruation became more regular, and she became pregnant and delivered a healthy baby girl.

Conclusions

The genotypes may be p.I173N homozygous or p.I173N/c.1451-1452delGGinsC heterozygous, both mutations could be pathogenic. This complex combination of mutations has not been reported or studied before. Through the report and analysis of this genotype, the content of CAH gene bank is enriched and the misdiagnosis rate of CAH is reduced.
Validation of a questionnaire exploring patient attitudes towards bedside teaching
Authors: Carey MO , O’Riordan N , Carty M , Ivers M , Taylor LK , Higgins MF
Published: March 2022

Background

Bedside teaching (BST) facilitates medical education and has reduced in practice, often due to patient-related concerns. This study aimed to validate a questionnaire exploring patients attitudes towards BST.

Methods

International guidelines for questionnaire development were followed. Seven steps were included: literature review, patient interviews, development of clear and understandable items, expert validation, cognitive interviewing and pilot testing. Statistical analyses included exploratory factor analysis, internal consistency, investigation of demographic influences and discriminant validity across subscales.

Results

Following the literature review, 32 interviews were conducted. Potential items were developed, reviewed and adapted. Experts in medical education and statistics reviewed the draft questionnaire. Fifteen patients consented to cognitive testing and 401 consenting patients completed the final version. The median age of participants was 35 years of age (range: 18 to 70 years). Participants included women attending for antenatal (40%), postnatal (32%) and gynaecology issues (28%). Just under one third (29%) had taken part in medical student teaching previously.

Statistical analyses found a two-factor solution, consisting of Educate medical professionals and Conditions for participation subscales with good internal consistency; responses did not vary by age or education. Participants who had opted-in for teaching in the ward and bedside endorsed higher levels of Educate medical professionals, suggesting discriminant validity.

A majority of patients (> 92%) reported that they were happy to be involved in BST. Patients believed that they should not be asked to participate in BST should they feel stressed or unwell (68.2%).

Conclusion

This study shows extensive patient support for BST, independent of age or education. The desire to educate is a strong motivating factor. This strong support by patients for BST is an area that medical schools and universities can potentially develop. Future versions of this questionnaire may include virtual bedside teaching, in the context of social distancing.
Universal healthcare coverage, patients' rights, and nurse-patient communication: a critical review of the evidence
Authors: Kwame Abukari , Petrucka Pammla M.
Published: March 2022

The Sustainable Development Goals adopted by world leaders on September 25, 2015, aimed to end poverty and hunger, promote gender equity, empower women and girls, and ensure human dignity and equality by all human beings in a healthy environment. These development goals were premised on international human rights norms and institutions, thereby acknowledging the relevance of human rights in achieving each goal. Particularly, sustainable development goal 3, whose objective is to achieve universal health coverage, enhance healthy lives, and promote well-being for all, implicitly recognizes the right to health as crucial. Our focus in this paper is to discuss how promoting patients’ rights and enhancing effective nurse-patient communication in the healthcare setting is a significant and necessary way to achieve universal health coverage. Through a critical review of the empirical research evidence, we demonstrated that enhancing patients’ rights and effect nurse-patient communication will promote people-centered care, improve patients’ satisfaction of care outcomes, increase utilization of care services, and empower individuals and families to self-advocate for their health. These steps directly impact primary healthcare strategies and the social determinants of health as core components to achieving universal health coverage. We argue that without paying attention to the human rights dimensions or employing human rights strategies, implementing the other efforts will be inadequate and unsustainable in protecting the poorest and most vulnerable populations in the achievement of goal 3.
hsa-miR-875-5p inhibits tumorigenesis and suppresses TGF-β signalling by targeting USF2 in gastric cancer
Authors: Gao Shenshuo , Zhang Zhikai , Wang Xubin , Ma Yan , Li Chensheng , Liu Hongjun , Jing Changqing , Li Leping , Guo Xiaobo
Published: March 2022

Background

Gastric cancer (GC) is one of the most common malignancies, and an increasing number of studies have shown that its pathogenesis is regulated by various miRNAs. In this study, we investigated the role of miR-875-5p in GC.

Methods

The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA qRT–PCR. The effect of miR-875-5p on GC proliferation was determined by Cell Counting Kit-8 (CCK-8) proliferation and 5-ethynyl-2′-deoxyuridine (EdU) assays. Migration and invasion were examined by transwell migration and invasion assays as well as wound healing assays. The interaction between miR-875-5p and its target gene upstream stimulatory factor 2(USF2) was verified by dual luciferase reporter assays. The effects of miR-875-5p in vivo were studied in xenograft nude mouse models. Related proteins were detected by western blot.

Results

The results showed that miR-875-5p inhibited the proliferation, migration and invasion of GC cells in vitro and inhibited tumorigenesis in vivo. USF2 was proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracted the effects of miR-875-5p inhibitor. Overexpression of miR-875-5p could inhibit proliferation, migration and invasion and suppress the TGF-β signalling pathway by downregulating USF2.

Conclusions

MiR-875-5p can inhibit the progression of GC by directly targeting USF2. And in the future, miR-875-5p is expected to be a potential target for GC diagnosis and treatment.
Microbiota medicine: towards clinical revolution
Authors: Gebrayel Prisca , Nicco Carole , Al Khodor Souhaila , Bilinski Jaroslaw , Caselli Elisabetta , Comelli Elena M. , Egert Markus , Giaroni Cristina , Karpinski Tomasz M. , Loniewski Igor , Mulak Agata , Reygner Julie , Samczuk Paulina , Serino Matteo , Sikora Mariusz , Terranegra Annalisa , Ufnal Marcin , Villeger Romain , Pichon Chantal , Konturek Peter , Edeas Marvin
Published: March 2022

The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge.
Photobiomodulation as a treatment for dermatitis caused by chemoradiotherapy for squamous cell anal carcinoma: case report and literature review
Authors: Hottz Fabiana , Herchenhorn Daniel , Lenzi Juliana , Andrade Juliana , Freire Vinicius , Pinho Pedro
Published: March 2022

In-field dermatitis is a severe and common adverse effect of radiation therapy, that can cause significant pain and treatment interruptions in patients with squamous cell anal carcinoma (SCAC) being treated with radical chemoradiation protocols. There are no established therapies for the treatment of radiation induced dermatitis. Photobiomodulation (PBM) is an effective and low-cost treatment for radiation induced mucositis, but have recently been explored to treat in-field dermatitis. We present a case report of the successful use of PBM for the treatment of dermatitis in the anal area in a patient with SCAC treated with concomitant chemoradiation with curative intent and follow with a literature review of the recent advances and possibilities of the use of PBM as a promising strategy. PBM therapy proved to be efficient in the radiodermatitis treatment, both in relieving the symptoms and controlling dermatitis, in addition to improving the patient's quality of life.
Effect of central sensitization on dizziness-related symptoms of persistent postural-perceptual dizziness
Authors: Hashimoto Kazuaki , Takeuchi Takeaki , Ueno Takayuki , Suka Shunsuke , Hiiragi Miki , Yamada Maya , Koyama Akiko , Nakamura Yuzo , Miyakoda Jun , Hashizume Masahiro
Published: March 2022

Background

Persistent postural-perceptual dizziness (PPPD) is a chronic functional dizziness symptom triggered by psychological stress, but its pathophysiology is unknown. Central sensitization is considered the cause of functional diseases, such as medically unexplained symptoms, and is a psychosocially affected condition. However, the association between dizziness symptoms in PPPD and central sensitization remains unclear. Thus, we conducted a cross-sectional study on the relation between dizziness symptoms and central sensitization in PPPD.

Methods

We recruited 61 outpatients with dizziness who met the PPPD diagnostic criteria. In addition to the evaluation of dizziness symptoms using the Dizziness Handicap Inventory, the participants were evaluated using the Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, and Central Sensitization Inventory (CSI). A CSI score of 40 or higher was defined as central sensitization syndrome (CSS), and the severity of each condition in CSS and non-CSS participants was compared. We also evaluated the association between dizziness symptoms and central sensitization and coexisting symptoms using linear multiple regression analysis.

Results

We analyzed the data of 50 valid responses (valid response rate of 82.0 percent). Compared with the non-CSS group, the CSS group had a higher degree of disability owing to dizziness and a higher rate of complications of anxiety and depression. The regression analysis results showed that the severity of central sensitization was a related factor that could enhance the dizziness symptoms of PPPD.

Conclusions

Central sensitization may affect the dizziness symptoms of PPPD as an exacerbating factor.
Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3, open-label trial
Authors: Zhao Ke , Lin Ren , Fan Zhiping , Chen Xiaoyong , Wang Yu , Huang Fen , Xu Na , Zhang Xi , Zhang Xin , Xuan Li , Wang Shunqing , Lin Dongjun , Deng Lan , Nie Danian , Weng Jianyu , Li Yonghua , Zhang Xiaohui , Li Yuhua , Xiang A. P. , Liu Qifa
Published: March 2022

Background

Steroid-resistant (SR) acute graft-versus-host disease (aGVHD) lacks standard second-line treatment. Mesenchymal stromal cells (MSCs) have potential efficacy in SR aGVHD. We aimed to assess the efficacy and safety of MSCs combined with basiliximab and calcineurin inhibitor as second-line therapy for SR aGVHD.

Methods

A randomized phase 3 trial involved 203 SR aGVHD patients at nine centers in China (September 2014–March 2019). Participants were randomized at a 1:1 ratio to receive second-line therapy with (n = 101) or without (n = 102) MSCs. The primary endpoint was the overall response (OR) at day 28. Secondary and safety endpoints included durable OR at day 56, failure-free survival, overall survival (OS), chronic GVHD (cGVHD), infection, hematological toxicity and relapse.

Results

Of 203 patients, 198 (97.5%; mean age, 30.1 years; 40.4% women) completed the study. The OR at day 28 was higher in the MSC group than the control group (82.8% [82 patients] vs. 70.7% [70]; odds ratio, 2.00; 95% confidence interval [CI], 1.01–3.94; P = 0.043). The durable OR at day 56 was also higher in the MSC group (78.8% [78 patients] vs. 64.6% [64]; odds ratio, 2.02; 95% CI, 1.08–3.83; P = 0.027). The median failure-free survival was longer in the MSC group compared with control (11.3 months vs. 6.0 months; hazard ratio (HR) 0.68; 95% CI, 0.48–0.95, P = 0.024). The 2-year cumulative incidence of cGVHD was 39.5% (95% CI, 29.3–49.4%) and 62.7% (51.4–72.1%) in the MSC and control groups (HR 0.55, 95% CI, 0.36–0.84; P = 0.005). Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections (65 [65.7%] in the MSC group vs. 78 [78.8%] in the control group) and hematological toxicity (37 [37.4%] vs. 53 [53.5%]). The 3-year cumulative incidence of tumor relapse was 10.1% (95% CI, 5.2–17.1) and 13.5% (7.5–21.2%) in the MSC and control groups, respectively (HR 0.75, 95% CI, 0.34–1.67, P = 0.610).

Conclusions

MSCs plus second-line treatments increase the efficacy of SR aGVHD, decrease drug toxicity of second-line drugs and cGVHD without increasing relapse, and are well-tolerated. MSCs could be recommended as a second-line treatment option for aGVHD patients.

Trial registration clinicaltrials.gov identifier: NCT02241018. Registration date: September 16, 2014, https://clinicaltrials.gov/ct2/show/NCT02241018.
Limitations of the ARDS criteria during high-flow oxygen or non-invasive ventilation: evidence from critically ill COVID-19 patients
Authors: Hultström Michael , Hellkvist Ola , Covaciu Lucian , Fredén Filip , Frithiof Robert , Lipcsey Miklós , Perchiazzi Gaetano , Pellegrini Mariangela
Published: March 2022

Background

The ratio of partial pressure of arterial oxygen to inspired oxygen fraction (PaO2/FIO2) during invasive mechanical ventilation (MV) is used as criteria to grade the severity of respiratory failure in acute respiratory distress syndrome (ARDS). During the SARS-CoV2 pandemic, the use of PaO2/FIO2 ratio has been increasingly used in non-invasive respiratory support such as high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The grading of hypoxemia in non-invasively ventilated patients is uncertain. The main hypothesis, investigated in this study, was that the PaO2/FIO2 ratio does not change when switching between MV, NIV and HFNC.

Methods

We investigated respiratory function in critically ill patients with COVID-19 included in a single-center prospective observational study of patients admitted to the intensive care unit (ICU) at Uppsala University Hospital in Sweden. In a steady state condition, the PaO2/FIO2 ratio was recorded before and after any change between two of the studied respiratory support techniques (i.e., HFNC, NIV and MV).

Results

A total of 148 patients were included in the present analysis. We find that any change in respiratory support from or to HFNC caused a significant change in PaO2/FIO2 ratio. Changes in respiratory support between NIV and MV did not show consistent change in PaO2/FIO2 ratio. In patients classified as mild to moderate ARDS during MV, the change from HFNC to MV showed a variable increase in PaO2/FIO2 ratio ranging between 52 and 140 mmHg (median of 127 mmHg). This made prediction of ARDS severity during MV from the apparent ARDS grade during HFNC impossible.

Conclusions

HFNC is associated with lower PaO2/FIO2 ratio than either NIV or MV in the same patient, while NIV and MV provided similar PaO2/FIO2 and thus ARDS grade by Berlin definition. The large variation of PaO2/FIO2 ratio indicates that great caution should be used when estimating ARDS grade as a measure of pulmonary damage during HFNC.
StrainGE: a toolkit to track and characterize low-abundance strains in complex microbial communities
Authors: van Dijk Lucas R. , Walker Bruce J. , Straub Timothy J. , Worby Colin J. , Grote Alexandra , Schreiber Henry L. , Anyansi Christine , Pickering Amy J. , Hultgren Scott J. , Manson Abigail L. , Abeel Thomas , Earl Ashlee M.
Published: March 2022

Human-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the difficulties of studying them. We introduce the Strain Genome Explorer (StrainGE) toolkit, which deconvolves strain mixtures and characterizes component strains at the nucleotide level from short-read metagenomic sequencing with higher sensitivity and resolution than other tools. StrainGE is able to identify strains at 0.1x coverage and detect variants for multiple conspecific strains within a sample from coverages as low as 0.5x.
Effectiveness of aloe fomentation for nipple-related complications during the early puerperium period: a randomized, controlled, interventional study
Authors: Tateoka Yumiko
Published: March 2022

Objective

Nipple-related complications are major factors that prevent breastfeeding for many new mothers. Hence, we tested the effects of aloe arborescens fomentation applied to the nipples as a treatment for nipple-related complications.

Results

This study included 60 women who breastfed for the first time on day 1 after delivery. Every 24 h, all women breastfed six times and bottle-fed two times (at night). Women were classified into an intervention group (aloe arborescens fomentation) and a control group (no treatment). Aloe fomentation was applied after breastfeeding six times per day. We observed the nipples three times per day for 5 days after delivery. The most common nipple-related complication in this study was redness. A significant decrease was observed for women in the intervention group.

Trial Registration Retrospectively Registered to registry: UMIN; Registration no.: UMIN000044514; Registered on: 11th June 2021.
The effect of maternal intravenous hydration on amniotic fluid index in oligohydramnios
Authors: Azarkish Fatemeh , Janghorban Roksana , Bozorgzadeh Shirin , Arzani Abedeh , Balouchi Rahemeh , Didehvar Mahnaz
Published: March 2022

Objective

Assessing amniotic fluid determines an important dimension of fetal health. Significant relationships of oligohydramnios, which occurs in 1–2% of pregnancies, with abnormal pregnancy outcomes such as intrauterine growth retardation (IUGR), fetal anomalies, umbilical cord compression, fetal distress, preterm childbirth, meconium-stained amniotic fluid, perinatal mortality and cesarean section necessitate the measurement of amniotic fluid volume in many prenatal fetal health assessments.

Amniotic fluid volume may significantly fluctuate between different gestational ages. Reduced uteroplacental perfusion can cause oligohydramnios by decreasing fetal renal blood flow and urine output. The appropriate management of isolated term oligohydramnios (ITO) is controversial. This study was performed aimed to assess the effect of maternal intravenous hydration on amniotic fluid index in oligohydramnios.

Result

Forty-eight hours after completing fluid therapy, statistically significant differences were observed in the mean AFI in the intervention group (4.06 ± 0.33) and the control group (3.61 ± 0.35) (P < 0.0001) and also between the intervention group (0.532 ± 0.45) and the controls (−0.036 ± 0.18) (P < 0.0001).

Conclusion

The results of the present study suggested that maternal intravenous hydration significantly increases AFI in women with oligohydramnios.
Changes of radiological examination volumes over the course of the COVID-19 pandemic: a comprehensive analysis of the different waves of infection
Authors: Fleckenstein Florian Nima , Maleitzke Tazio , Böning Georg , Kahl Vinzent , Petukhova-Greenstein Alexandra , Kucukkaya Ahmet Said , Gebauer Bernhard , Hamm Bernd , Aigner Annette
Published: March 2022

Objectives

Data from radiological departments provide important information on overall quantities of medical care provided. With this study we used a comprehensive analysis of radiological examinations as a surrogate marker to quantify the effect of the different COVID-19 waves on medical care provided.

Methods

Radiological examination volumes during the different waves of infection were compared among each other as well as to time-matched control periods from pre-pandemic years using a locally weighted scatterplot smoothing as well as negative binominal regression models.

Results

A total of 1,321,119 radiological examinations were analyzed. Examination volumes were reduced by about 10% over the whole study period (IRR = 0.90; 95% CI 0.89–0.92), with a focus on acute medical care (0.84; 0.83–0.85) and outpatients (0.93: 0.90–0.97). When compared to wave 1, examination volumes were about 17% higher during wave 2 (1.17; 1.10–1.25), and 33% higher in wave 3 of the pandemic (1.33; 1.24–1.42).

Conclusions

This study shows the severe effect of COVID-19 pandemic and related shutdown measures on overall provided medical care as measured by radiological examinations. When compared, the decrease of medical care was more pronounced in the earlier waves of the pandemic.
Neurogenesis in the neonatal rat hippocampus is regulated by sexually dimorphic epigenetic modifiers
Authors: Stockman S. L. , Kight K. E. , Bowers J. M. , McCarthy M. M.
Published: March 2022

Background

Neurogenesis in the hippocampus endures across the lifespan but is particularly prolific during the first postnatal week in the developing rodent brain. The majority of new born neurons are in the dentate gyrus (DG). The number of new neurons born during the first postnatal week in the DG of male rat pups is about double the number in females. In other systems, the rate of cell proliferation is controlled by epigenetic modifications in stem cells. We, therefore, explored the potential impact of DNA methylation and histone acetylation on cell genesis in the developing DG of male and female rats.

Methods

Cell genesis was assessed by quantification of BrdU + cells in the DG of neonatal rats following injections on multiple days. Methylation and acetylation were manipulated pharmacologically by injection of well vetted drugs. DNA methylation, histone acetylation and associated enzyme activity were measured using commercially available colorimetric assays. mRNA was quantified by PCR. Multiple group comparisons were made by one- or two-way ANOVA followed by post-hoc tests controlling for multiple comparisons. Two groups were compared by t test.

Results

We found higher levels of DNA methylation in male DG and treatment with the DNA methylating enzyme inhibitor zebularine reduced the methylation and correspondingly reduced cell genesis. The same treatment had no impact on either measure in females. By contrast, treatment with a histone deacetylase inhibitor, trichostatin-A, increased histone acetylation in the DG of both sexes but increased cell genesis only in females. Females had higher baseline histone deacetylase activity and greater inhibition in response to trichostatin-A treatment. The mRNA levels of the proproliferative gene brain-derived neurotrophic factor were greater in males and reduced by inhibiting both DNA methylation and histone deacetylation only in males.

Conclusions

These data reveal a sexually dimorphic epigenetically based regulation of neurogenesis in the DG but the mechanisms establishing the distinct regulation involving DNA methylation in males and histone acetylation in females is unknown.
MolData, a molecular benchmark for disease and target based machine learning
Authors: Keshavarzi Arshadi Arash , Salem Milad , Firouzbakht Arash , Yuan Jiann Shiun
Published: March 2022

Deep learning’s automatic feature extraction has been a revolutionary addition to computational drug discovery, infusing both the capabilities of learning abstract features and discovering complex molecular patterns via learning from molecular data. Since biological and chemical knowledge are necessary for overcoming the challenges of data curation, balancing, training, and evaluation, it is important for databases to contain information regarding the exact target and disease of each bioassay. The existing depositories such as PubChem or ChEMBL offer the screening data for millions of molecules against a variety of cells and targets, however, their bioassays contain complex biological descriptions which can hinder their usage by the machine learning community. In this work, a comprehensive disease and target-based dataset is collected from PubChem in order to facilitate and accelerate molecular machine learning for better drug discovery. MolData is one the largest efforts to date for democratizing the molecular machine learning, with roughly 170 million drug screening results from 1.4 million unique molecules assigned to specific diseases and targets. It also provides 30 unique categories of targets and diseases. Correlation analysis of the MolData bioassays unveils valuable information for drug repurposing for multiple diseases including cancer, metabolic disorders, and infectious diseases. Finally, we provide a benchmark of more than 30 models trained on each category using multitask learning. MolData aims to pave the way for computational drug discovery and accelerate the advancement of molecular artificial intelligence in a practical manner. The MolData benchmark data is available at https://GitHub.com/Transilico/MolData as well as within the additional files.
Where are race-based oral health inequities bound? Protocol for a systematic review on interventions to tackle racial injustice in dental outcomes
Authors: Bastos João L. , Constante Helena M. , Schuch Helena S. , Haag Dandara G. , Nath Sonia , Celeste Roger K. , Guarnizo-Herreño Carol C. , McCallum Mary J. , Jamieson Lisa M.
Published: March 2022

Background

Only three literature reviews have assessed the impact of interventions on the reduction of racial inequities in general health to date; none has drawn from attempts at promoting racial oral health equity. This protocol aims to increase transparency and reduce the potential for bias of an ongoing systematic review conceived to answer the following questions: Are there any interventions to mitigate racial oral health inequities or improve the oral health of racially marginalized groups? If so, how successful have they been at promoting racial oral health equity? How do conclusions of previous reviews change by taking the findings of oral health interventions into account?

Methods

Reviewed studies must deploy interventions to reduce racial gaps or promote the oral health of groups oppressed along ancestral and/or cultural lines. We will analyze randomized clinical trials, natural experiments, pre-post studies, and observational investigations that emulate controlled experiments by assessing interactions between race and potentially health-enhancing interventions. Either clinically assessed or self-reported oral health outcomes will be considered by searching for original studies in MEDLINE, LILACS, PsycInfo, SciELO, Web of Science, Scopus, and Embase from their earliest records to March 2022. Upon examining abstracts of conference proceedings, trial registries, reports of related stakeholder organizations, as well as contacting researchers for unpublished data, we will identify studies in the grey literature. If possible, we will carry out a meta-analysis with subgroup and sensitivity analysis, including formal meta-regression, to address potential heterogeneity and inconsistency among selected studies.

Discussion

Conducting a systematic review of interventions to mitigate racial oral health inequities is crucial for determining which initiatives work best and under which conditions they succeed. Such knowledge will help consolidate an evidence base that may be used to inform policy and practice against persistent and pervasive racial inequities in general and oral health.

Systematic review registration

This protocol has been registered at the International Prospective Register of Systematic Reviews, under the identification number CRD42021261450.
Some new results and inequalities for subsequences of Nörlund logarithmic means of Walsh–Fourier series
Authors: Baramidze David , Persson Lars-Erik , Singh Harpal , Tephnadze George
Published: March 2022

We prove that there exists a martingale $f\in H_{p} $
f
∈

H
p

such that the subsequence $\{L_{2^{n}}f \}$
{

L

2
n

f
}
of Nörlund logarithmic means with respect to the Walsh system are not bounded from the martingale Hardy spaces $H_{p}$

H
p

to the space $weak-L_{p} $
w
e
a
k
−

L
p

for $0< p<1 $
0
<
p
<
1
. We also prove that for any $f\in L_{p}$
f
∈

L
p

, $p\geq 1 $
p
≥
1
, $L_{2^{n}}f$

L

2
n

f
converge to f at any Lebesgue point x. Moreover, some new related inequalities are derived.
Antimicrobial resistance (AMR) in COVID-19 patients: a systematic review and meta-analysis (November 2019–June 2021)
Authors: Kariyawasam Ruwandi M. , Julien Danielle A. , Jelinski Dana C. , Larose Samantha L. , Rennert-May Elissa , Conly John M. , Dingle Tanis C. , Chen Justin Z. , Tyrrell Gregory J. , Ronksley Paul E. , Barkema Herman W.
Published: March 2022

Background

Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR).

Objectives

We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings.

Methods

We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences.

Results

Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8–40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1–0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism.

Conclusions

During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.
Emergency caesarean section in a patient with pygomelia: a curious tale of a misidentified “tail”—a case report
Authors: Reena  , Singh Rahul , Vikram Ashutosh
Published: March 2022

Background

Polymelia or congenital duplication of the lower limb is a rare occurrence. This congenital duplication when occurring in the region of the buttocks is known as pygomelia. Its appearance can even mimic a human tail or pseudotail.

Case presentation

A 22-year-old primigravida posted for emergency caesarean section was found to have a tail-like structure attached to her lower back. Pre-operative imaging of that appendage to rule out spinal dysraphism was not done due to the need of emergency surgery and pregnant status of the patient. The patient received general anaesthesia for surgery, and in the follow-up, X-ray imaging was done which showed a hemipelvis and a femur bone in that appendage confirming the diagnosis of pygomelia.

Conclusions

In a rare occurrence of pygomelia, the exact nature can be identified by various imaging modalities. General anaesthesia was a safe choice in such a patient presenting for emergency caesarean section.
Parameter estimation and sensitivity analysis for a model of tumor–immune interaction in the presence of immunotherapy and chemotherapy
Authors: Elkaranshawy Hesham A. , Makhlouf Ahmed M.
Published: March 2022

A mathematical model has been utilized to examine the interaction between tumor cells and immune cells. In this model, the immune cells include natural killer cells, circulating lymphocytes, CD8+T cells, CD4+T cells, and cytokines. The model not only represents the traditional role of CD4+T cells in activating CD8+T cells but also illustrates its role in killing the tumor via the secretion of cytokines. Besides, treatments with both chemotherapy and immunotherapy are considered. However, since this model was not fitted to experimental data before, parameter estimation is performed to fit the model with experimental data, first. The estimation is validated to verify the correctness of the model using the experimental data for the tumor growth. Second, numerical experiments are performed using a set of human data. Results show the mutual relations between tumor cells, and body immune cells in the absence and in the presence of therapy. Results also show that CD4+T cells could play a crucial role in immunotherapy. Third, sensitivity analysis is performed by calculating the normalized sensitivity coefficients to identify the relative influence of body parameters on the tumor cell population. The obtained results provide a tool to identify which parameters should be increased or decreased before treatment to get the optimal immune response.
Data-driven fast prestack structurally constrained inversion
Authors: Yang Yaming , Xia Xingtong , Yin Xingyao , Li Kun , Wang Jianli , Liu Hoagie
Published: March 2022

Classic multitrace inversion, such as structurally constrained inversion (SCI), tends to arrange seismic data trace by trace to introduce constraints that are more in line with the structure or reflection features. However, this strategy of rearranging seismic traces extensively increases the number of calculations, thereby limiting the wide application of SCI in prestack inversion. We have developed two improved prestack SCI algorithms that can simultaneously invert all seismic traces with structural constraints in a short time and substantially reduce the dependence on seismic data quality. The key to the proposed techniques lies in achieving structural constraints by introducing a Hadamard product operator without rearranging the seismic traces because it avoids the generation of large-scale and memory-intensive convolution matrices and structural constraint operators. We have deduced a corresponding fast algorithm and named it fast structurally constrained inversion. In addition because the quality of seismic data plays a decisive role in inversion, we further have developed a data-driven fast structurally constrained inversion (DFSCI) algorithm wherein a local crosscorrelation coefficient reflects the reliability of the local seismic data to a certain extent. Therefore, applying DFSCI to control the contribution of seismic data at each sampling point in the inversion can reduce the dependence of seismic data quality. The noise resistance capability and the spatial continuity of the proposed methods have been verified through numerical experiments and a field data example.
Antidepressant prescribing for adult people with an intellectual disability living in England
Authors: Branford David , Shankar Rohit
Published: March 2022

The prescribing of psychotropic medications for people with an intellectual disability has changed. In many locations across England, antidepressants have become the most widely prescribed psychotropic. In the context of the current NHS England STOMP programme to reduce inappropriate psychotropic prescribing for people with intellectual disability, there is an urgent need to understand whether this change reflects evidence-based use of the medications involved. There has been little analysis into the benefits or problems associated with the change and whether it is of concern. This paper offers a variety of possible explanations and opportunities to improve clinical practice and policy.
Towards personalised predictive psychiatry in clinical practice: an ethical perspective
Authors: Lane Natalie , Broome Matthew
Published: March 2022

Personalised prediction models promise to enhance the speed, accuracy and objectivity of clinical decision-making in psychiatry in the near future. This editorial elucidates key ethical issues at stake in the real-world implementation of prediction models and sets out practical recommendations to begin to address these.
Phase I Study of Safety, Tolerability, and Efficacy of Tebentafusp Using a Step-Up Dosing Regimen and Expansion in Patients With Metastatic Uveal Melanoma
Authors: Carvajal Richard D. , Nathan Paul , Sacco Joseph J. , Orloff Marlana , Hernandez-Aya Leonel F. , Yang Jessica , Luke Jason J. , Butler Marcus O. , Stanhope Sarah , Collins Laura , McAlpine Cheryl , Holland Chris , Abdullah Shaad E. , Sato Takami
Published: March 2022

PURPOSE

This phase I study aimed to define the recommended phase II dose (RP2D) of tebentafusp, a first-in-class T-cell receptor/anti-CD3 bispecific protein, using a three-week step-up dosing regimen, and to assess its safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity in patients with metastatic uveal melanoma (mUM).

METHODS

In this open-label, international, phase I/II study, HLA-A*02 or HLA-A*02:01+ patients with mUM received tebentafusp 20 μg once in week 1 and 30 μg once in week 2. Dose escalation (starting at 54 μg) began at week 3 in a standard 3 + 3 design to define RP2D. Expansion-phase patients were treated at the RP2D (20-30-68 μg). Blood and tumor samples were collected for pharmacokinetics/pharmacodynamics assessment, and treatment efficacy was evaluated for all patients with baseline efficacy data as of December 2017.

RESULTS

Between March 2016 and December 2017, 42 eligible patients who failed a median of two previous treatments were enrolled: 19 in the dose escalation cohort and 23 in an initial dose expansion cohort. Of the dose levels investigated, 68 μg was identified as the RP2D. Most frequent treatment-emergent adverse events regardless of attribution were pyrexia (91%), rash (83%), pruritus (83%), nausea (74%), fatigue (71%), and chills (69%). Toxicity attenuated following the first three doses. The overall response rate was 11.9% (95% CI, 4.0 to 25.6). With a median follow-up of 32.4 months, median overall survival was 25.5 months (range, 0.89-31.1 months) and 1-year overall survival rate was 67%. Treatment was associated with increased tumor T-cell infiltration and transient increases in serum inflammatory mediators.

CONCLUSION

Using a step-up dosing regimen of tebentafusp allowed a 36% increase in the RP2D compared with weekly fixed dosing, with a manageable side-effect profile and a signal of efficacy in mUM.