bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel 1p13.2 deletion associates with neurodevelopmental disorders in a three-generation pedigree
Authors: Yu Lihua , Ding Hongke , Liu Min , Liu Ling , Zhang Qi , Lu Jian , Guo Fangfang , Zhang Yan
Published: May 2023

Background

A multitude of studies have highlighted that copy number variants (CNVs) are associated with neurodevelopmental disorders (NDDs) characterized by a wide range of clinical characteristics. Benefiting from CNV calling from WES data, WES has emerged as a more powerful and cost-effective molecular diagnostic tool, which has been widely used for the diagnosis of genetic diseases, especially NDDs. To our knowledge, isolated deletions on chromosome 1p13.2 are rare. To date, only a few patients were reported with 1p13.2 deletions and most of them were sporadic. Besides, the correlation between 1p13.2 deletions and NDDs remained unclear.

Case presentation

Here, we first reported five members in a three-generation Chinese family who presented with NDDs and carried a novel 1.41 Mb heterozygous 1p13.2 deletion with precise breakpoints. The diagnostic deletion contained 12 protein-coding genes and was observed to segregate with NDDs among the members of our reported family. Whether those genes contribute to the patient’s phenotypes is still inconclusive.

Conclusions

We hypothesized that the NDD phenotype of our patients was caused by the diagnostic 1p13.2 deletion. However, further in-depth functional experiments are still needed to establish a 1p13.2 deletion-NDDs relationship. Our study might supplement the spectrum of 1p13.2 deletion-NDDs.
Cell surface GRP78: a potential mechanism of therapeutic resistant tumors
Authors: Amaresan Rajalakshmi , Gopal Udhayakumar
Published: May 2023

GRP78 is a protein that acts as a chaperone within the endoplasmic reticulum (ER) and has multiple functions. It is induced by stress and abets cells from survival. Despite, multiple Stress conditions like ER, chronic psychological and nutritional stress, hypoxia, chemotherapy, radiation therapy, and drug resistance induce cell surface GRP78 (CS-GRP78) expression in cancer cells. Further, CS-GRP78 is associated with increased malignancy and resistance to anti-cancer therapies and is considered a high-value druggable target. Recent preclinical research suggests that targeting CS-GRP78 with anti-GRP78 monoclonal antibodies (Mab) in combination with other agents may be effective in reversing the failure of chemotherapy, radiotherapy, or targeted therapies and increasing the efficacy of solid tumors treatment. This article will review recent evidence on the role of CS-GRP78 in developing resistance to anti-cancer treatments and the potential benefits of combining anti-GRP78 Mab with other cancer therapies for specific patient populations. Furthermore, our limited understanding of how CS-GRP78 regulated in human studies is a major drawback for designing effective CS-GRP78-targeted therapies. Hence, more research is still warranted to translate these potential therapies into clinical applications.
Not all screens are created equal: examination of surface features and other physical properties of commonly used screen materials for smoking drugs
Authors: Diak Bradley J. , Miskovic Miroslav , Zurba Nadia , Beaumont Denise
Published: May 2023

Background

Brass screens are considered an essential part of the safer drug smoking/inhalation supplies and are widely distributed by harm reduction programs in Canada. However, the use of commercially available steel wools as screens for smoking crack cocaine remains a common practice among people who smoke drugs in Canada. Use of these steel wool materials is associated with different adverse effects on health. This study aims to determine what changes folding and heating have on several filter materials, including brass screens and commercially available steel wool products, and examine the implications of these changes on health of people who smoke drugs.

Methods

This study investigated the microscopic differences, studied by optical and scanning electron microscopy, between four screen and four steel wool filter materials used in a simulated drug consumption process. New materials were manipulated, compacted into its own Pyrex® straight stem using a push stick and then heated with a butane lighter simulating a common method in preparing drugs for consumption. The materials were studied in the as-received (new), as-pressed (compressed and inserted into the stem tube but without heating) and as-heated (compressed and inserted into the stem tube and heated with a butane lighter) conditions.

Results

The steel wool materials with the smallest wire thicknesses were found to be the easiest to prepare for pipe use, but degrade significantly during shaping and heating, making them wholly unsuitable as a safe filter material. In contrast the brass and stainless steel screen materials remain mostly unchanged by the simulated drug consumption process. After the stainless steel pellet screen, the Brass Impact 2.0 screen material had the best characteristics of the materials tested due to its mesh wire diameter, pitch, alloy choice and its pre-strained state.

Conclusion

Commonly used steel wool alternatives degrade during the handling and stem insertion, and heating the screens in the stem. Debris is generated by wool deformation on insertion and after heating that easily separates from the screen and can be inhaled during drug consumption. The brass and stainless steel screen materials are safer to use as they remain mostly stable during the simulated drug consumption process.
Factors associated with obstetric fistula among reproductive age women in Ethiopia: a community based case control study
Authors: Woldegebriel Ataklti Gebretsadik , Gebrehiwot Gebremedhin Gebreegziabiher , Desta Abraham Aregay , Ajemu Kiros Fenta , Berhe Asfawosen Aregay , Woldearegay Tewolde Wubayehu , Ghebremedhin Kiros Demoz , Bezabih Nega Mamo
Published: May 2023

Background

Obstetric fistula is a major public health concerns in Ethiopia. It is the most devastating cause of all maternal morbidities.

Method

Data from the 2016 Ethiopian Demographic Health Survey (EDHS) was analyzed. A community-based unmatched case control study was conducted. Seventy cases and 210 non cases were selected using random number table. Data were analyzed by using STATA statistical software version 14. Multivariable logistic regression model was applied to determine the factors associated with fistula.

Results

The majority of fistula cases were from rural residences. The multivariable statistical model showed that rural residence (Adjusted OR (AOR) = 5, 95% CI 4.26, 7.52), age at first marriage (AOR = 3.3, 95% CI 2.83, 4.60), poorest wealth index (AOR = 3.3, 95% CI 2.24, 5.01) and decision making for contraceptive use by husband alone (AOR = 1.3, 95% CI 1.124, 1.67) were factors significantly associated with obstetric fistula.

Conclusion

Age at first marriage, rural residence, poorest wealth index and decision making for contraceptive use by husband alone were significantly associated factors for obstetric fistula. Intervening on these factors will reduce the magnitude of obstetrics fistula. In this context there is in-need to improve on avoiding early marriage through awareness creation to the community and developing legal framework by the policymakers. Furthermore, information about the joint decision making to use contraceptives should be disseminated though mass-media and interpersonal channels.
Associations between circulating cell-free mitochondrial DNA, inflammatory markers, and cognitive and physical outcomes in community dwelling older adults
Authors: Nidadavolu Lolita S. , Feger Danielle , Chen Diefei , Wu Yuqiong , Grodstein Francine , Gross Alden L. , Bennett David A. , Walston Jeremy D. , Oh Esther S. , Abadir Peter M.
Published: May 2023

Background

Dementia and frailty are common age-related syndromes often linked to chronic inflammation. Identifying the biological factors and pathways that contribute to chronic inflammation is crucial for developing new therapeutic targets. Circulating cell-free mitochondrial DNA (ccf-mtDNA) has been proposed as an immune stimulator and potential predictor of mortality in acute illnesses. Dementia and frailty are both associated with mitochondrial dysfunction, impaired cellular energetics, and cell death. The size and abundance of ccf-mtDNA fragments may indicate the mechanism of cell death: long fragments typically result from necrosis, while short fragments arise from apoptosis. We hypothesize that increased levels of necrosis-associated long ccf-mtDNA fragments and inflammatory markers in serum are linked to declines in cognitive and physical function, as well as increased mortality risk.

Results

Our study of 672 community-dwelling older adults revealed that inflammatory markers (C-Reactive Protein, soluble tumor necrosis factor alpha, tumor necrosis factor alpha receptor 1 [sTNFR1], and interleukin-6 [IL-6]) positively correlated with ccf-mtDNA levels in serum. Although cross-sectional analysis revealed no significant associations between short and long ccf-mtDNA fragments, longitudinal analysis demonstrated a connection between higher long ccf-mtDNA fragments (necrosis-associated) and worsening composite gait scores over time. Additionally, increased mortality risk was observed only in individuals with elevated sTNFR1 levels.

Conclusion

In a community dwelling cohort of older adults, there are cross-sectional and longitudinal associations between ccf-mtDNA and sTNFR1 with impaired physical and cognitive function and increased hazard of death. This work suggests a role for long ccf-mtDNA as a blood-based marker predictive of future physical decline.
Extracellular vesicle-microRNAs mediated response of bovine ovaries to seasonal environmental changes
Authors: Gad Ahmed , Joyce Kamryn , Menjivar Nico Graham , Heredia Daniella , Rojas Camila Santos , Tesfaye Dawit , Gonella-Diaza Angela
Published: May 2023

Background

Among the various seasonal environmental changes, elevated ambient temperature during the summer season is a main cause of stress in dairy and beef cows, leading to impaired reproductive function and fertility. Follicular fluid extracellular vesicles (FF-EVs) play an important role in intrafollicular cellular communication by, in part, mediating the deleterious effects of heat stress (HS). Here we aimed to investigate the changes in FF-EV miRNA cargoes in beef cows in response to seasonal changes: summer (SUM) compared to the winter (WIN) season using high throughput sequencing of FF-EV-coupled miRNAs. In addition to their biological relevance, the potential mechanisms involved in the packaging and release of those miRNAs as a response to environmental HS were elucidated.

Results

Sequencing analysis revealed that an average of 6.6% of the EV-RNA mapped reads were annotated to bovine miRNAs. Interestingly, miR-148a, miR-99a-5p, miR-10b, and miR-143 were the top four miRNAs in both groups accounting for approximately 52 and 62% of the total miRNA sequence reads in the SUM and WIN groups, respectively. A group of 16 miRNAs was up-regulated and 8 miRNAs were down-regulated in the SUM compared to the WIN group. Five DE-miRNAs (miR-10a, miR-10b, miR-26a, let-7f, and miR-1246) were among the top 20 expressed miRNA lists. Sequence motif analysis revealed the appearance of two specific motifs in 13 out of the 16 upregulated miRNAs under HS conditions. Both motifs were found to be potentially bonded by specific RNA binding proteins including Y-box binding proteins (YBX1 and YBX2) and RBM42.

Conclusion

Our findings indicate that FF EV-coupled miRNA profile varies under seasonal changes. These miRNAs could be a good indicator of the cellular mechanism in mediating HS response and the potential interplay between miRNA motifs and RNA binding proteins can be one of the mechanisms governing the packaging and release of miRNAs via EVs to facilitate cellular survival.
Genomic hallmarks and therapeutic implications of G0 cell cycle arrest in cancer
Authors: Wiecek Anna J. , Cutty Stephen J. , Kornai Daniel , Parreno-Centeno Mario , Gourmet Lucie E. , Tagliazucchi Guidantonio Malagoli , Jacobson Daniel H. , Zhang Ping , Xiong Lingyun , Bond Gareth L. , Barr Alexis R. , Secrier Maria
Published: May 2023

Background

Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown.

Results

We develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintainTP53integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal geneCEP89as a modulator of proliferation and G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data.

Conclusions

We propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state.
Clinical utility of periodic reinterpretation of CNVs of uncertain significance: an 8-year retrospective study
Authors: Ravel Jean-Marie , Renaud Mathilde , Muller Jean , Becker Aurélie , Renard Émeline , Remen Thomas , Lefort Geneviève , Dexheimer Mylène , Jonveaux Philippe , Leheup Bruno , Bonnet Céline , Lambert Laëtitia
Published: May 2023

Background

Array-CGH is the first-tier genetic test both in pre- and postnatal developmental disorders worldwide. Variants of uncertain significance (VUS) represent around 10~15% of reported copy number variants (CNVs). Even though VUS reanalysis has become usual in practice, no long-term study regarding CNV reinterpretation has been reported.

Methods

This retrospective study examined 1641 CGH arrays performed over 8 years (2010–2017) to demonstrate the contribution of periodically re-analyzing CNVs of uncertain significance. CNVs were classified using AnnotSV on the one hand and manually curated on the other hand. The classification was based on the 2020 American College of Medical Genetics (ACMG) criteria.

Results

Of the 1641 array-CGH analyzed, 259 (15.7%) showed at least one CNV initially reported as of uncertain significance. After reinterpretation, 106 of the 259 patients (40.9%) changed categories, and 12 of 259 (4.6%) had a VUS reclassified to likely pathogenic or pathogenic. Six were predisposing factors for neurodevelopmental disorder/autism spectrum disorder (ASD). CNV type (gain or loss) does not seem to impact the reclassification rate, unlike the length of the CNV: 75% of CNVs downgraded to benign or likely benign are less than 500 kb in size.

Conclusions

This study’s high rate of reinterpretation suggests that CNV interpretation has rapidly evolved since 2010, thanks to the continuous enrichment of available databases. The reinterpreted CNV explained the phenotype for ten patients, leading to optimal genetic counseling. These findings suggest that CNVs should be reinterpreted at least every 2 years.
How effective are anthocyanins on healthy modification of cardiometabolic risk factors: a systematic review and meta-analysis
Authors: Neyestani Tirang R. , Yari Zahra , Rasekhi Hamid , Nikooyeh Bahareh
Published: May 2023

Background

In this meta-analysis, findings from recent studies on the preventive properties of anthocyanins (ACN) against cardiovascular disease are summarized.

Methods

MEDLINE, PubMed, Embase, Cochrane Library, and Google Scholar were searched and 2512 studies were found in a preliminary search. After screening of titles and abstracts, 47 studies met the inclusion criteria (randomized clinical trial design and sufficient data of outcomes). Studies were excluded based on the following criteria: incomplete data; obscurely reported outcomes, or lack of control groups; and animal studies.

Results

The results showed that intervention with ACNs resulted in a significant decrease in body mass index ((MD),− 0.21; 95% CI, − 0.38, − 0.04; P < 0.001) and body fat mass (MD: − 0.3%, 95% CI − 0.42 to − 0.18%, p < 0.001). Pooled data comparing ACN with control showed statistically significant effect on fasting blood sugar and HbA1c. However, the reductions were significantly more in the subjects with type 2 diabetes and in those who used ACN as supplement/extract. The subgroup analysis test showed that there was a significant effect of ACN on triglyceride concentrations, total cholesterol, LDL-C and HDL-C concentrations in all subgroups of participants (with vs. without dyslipidemia at baseline) and intervention type (supplement/extract vs. food). However, we did not observe any significant effect on apo A and apo B concentrations.

Conclusions

ACN intake in the forms of natural foods and supplements can induce healthy changes in body fat mass, glycemic and lipidemic status and these effects are more prominent in the subjects with above-normal values. This meta-analysis was registered at http://www.crd.york.ac.uk/Prospero (Registration no. CRD42021286466).
Associations of metabolic syndrome, its severity with cognitive impairment among hemodialysis patients
Authors: Yang Yuqi , Li Qian , Long Yanjun , Yuan Jing , Zha Yan
Published: May 2023

Background

In the general population, metabolic syndrome (MetS) is associated with increased risk of cognitive impairment, including global and specific cognitive domains. These associations are not well studied in patients undergoing hemodialysis and were the focus of the current investigation.

Methods

In this multicenter cross-sectional study, 5492 adult hemodialysis patients (3351 men; mean age: 54.4 ± 15.2 years) treated in twenty-two dialysis centers of Guizhou, China were included. The Mini-Mental State Examination (MMSE) was utilized to assess mild cognitive impairment (MCI). MetS was diagnosed with abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. Multivariate logistic and linear regression models were used to examine the associations of MetS, its components, and metabolic scores with the risk of MCI. Restricted cubic spline analyses were performed to explore the dose–response associations.

Results

Hemodialysis patients had a high prevalence of MetS (62.3%) and MCI (34.3%). MetS was positively associated with MCI risk with adjusted ORs of 1.22 [95% confidence interval (CI) 1.08–1.37, P = 0.001]. Compared to no MetS, adjusted ORs for MCI were 2.03 (95% CI 1.04–3.98) for 22.51 (95% CI 1.28–4.90) for 3, 2.35 (95% CI 1.20–4.62) for 4, and 2.94 (95% CI 1.48–5.84) for 5 components. Metabolic syndrome score, cardiometabolic index, and metabolic syndrome severity score were associated with increased risk of MCI. Further analysis showed that MetS was negatively associated with MMSE score, orientation, registration, recall and language (P < 0.05). Significant interaction effect of sex (P for interaction = 0.012) on the MetS-MCI was observed.

Conclusion

Metabolic syndrome was associated with MCI in hemodialysis patients in a positive dose–response effect.
The northeastern Algeria hydrothermal system: gravimetric data and structural implication
Authors: Bayou Yasser , Abtout Abdeslam , Renaut Rosemary A. , Bouyahiaoui Boualem , Maouche Said , Vatankhah Saeed , Berguig Mohamed Cherif
Published: May 2023

The Tell Atlas of Algeria has a huge potential for hydrothermal energy from over 240 thermal springs with temperatures up to $$98^\circ$$

98
∘

C in the Guelma area. The most exciting region is situated in the northeastern part which is known to have the hottest hydrothermal systems. In this work, we use a high-resolution gravity study to identify the location and origin of the hot water, and how it reaches the surface. Gravimetric data analysis shows the shapes of the anomalies arising due to structures at different subsurface depths. The calculation of the energy spectrum for the data also showcases the depths of the bodies causing anomalies. 3D-Euler deconvolution is applied to estimate the depths of preexisting tectonic structures (faults). These preprocessing steps assist with assessing signal attenuation that impacts the Bouguer anomaly map. The residual anomaly is used in a three-dimensional inversion to provide a subsurface density distribution model that illustrates the locations of the origin of the dominant subsurface thermal systems. Overall, the combination of these standard processing steps applied to the measurements of gravity data at the surface provides new insights about the sources of the hydrothermal systems in the Hammam Debagh and Hammam Ouled Ali regions. Faults that are key to the water infiltrating from depth to the surface are also identified. These represent the pathway of the hot water in the study area.
Magma ascent and degassing processes of the 2011 and 2017–18 eruptions of Shinmoedake in Kirishima volcano group, Japan, based on petrological characteristics and volatile content of magmas
Authors: Saito Genji , Oikawa Teruki , Ishizuka Osamu
Published: May 2023

The eruption activity of Shinmoedake in the Kirishima volcanic group of Japan resumed in 2017–18, following a quiet period during 2011–17. Subplinian eruptions preceded lava effusion in 2011; however, no subplinian eruption occurred during 2017–18. Petrological studies and melt inclusion analyses were conducted to investigate the ascent and degassing of the magma to understand the cause of the different eruption styles. Chemical analysis of the melt inclusions from the 2011 eruption indicates that mafic magma with high volatile content (6.2 wt% H2O, 0.25–1.4 wt% CO2) ascended into the shallow felsic magma (1.9–3.7 wt% H2O, 0.025–0.048 wt% CO2) at depths of 5–6 km. Calculations indicate that the mafic magmas were of lower density (1717–1835 kg m−3) than the felsic magma (2264–2496 kg m−3) at 125 MPa and that the two magmas were mixed. The 2011 mixed magma with high volatile content (4.0 wt% H2O, 0.14–0.70 wt% CO2) had a bubble volume of approximately 50 vol% at 50 MPa, which is likely to have caused the subplinian eruption. The whole-rock and chemical compositions of the plagioclase, clinopyroxene, and orthopyroxene phenocryst cores from 2018 and 2011 were similar, suggesting that the 2018 magma was a remnant of the 2011 magma. Chemical analyses of the groundmass from 2018 and the MELTS calculation indicate that the magma approached chemical equilibrium during 2011–18. Melt inclusion analyses and volcanic gas observation noted a lower bulk volatile content in the 2018 magma (2.1–3.0 wt% H2O, 0.087–0.10 wt% CO2) than that in the 2011 magma. Comparison of the degassed-magma volumes estimated from the S and Cl contents of the melt inclusions, SO2 flux and volcanic gas composition, and erupted-magma volume indicates that excess degassing has been occurring in the magma due to convection since February 2011, which may have decreased the volatile content of the magma. The relatively low volatile content meant that the 2018 magma could not erupt explosively and lava was instead erupted via effusion.

Graphical Abstract
Solar events and solar wind conditions associated with intense geomagnetic storms
Authors: Watari Shinichi , Nakamizo Aoi , Ebihara Yusuke
Published: May 2023

Intense magnetic storms pose a systemic threat to the electric power grid. In this study we examined the solar/interplanetary causes of such storms, their peak theoretical and observed intensities, and their occurrence frequency. Using coronal mass ejection (CME) and solar wind data, we selected the 18 intense magnetic storms from 1996 to 2021 with disturbance storm time (Dst) index of less than – 200 nT and analyzed solar events and solar wind conditions associated with them. Approximately 83% of the CMEs associated with the storms were full halo type and more than 83% of the flares associated with the storms were located within 30 degrees in longitude of solar central meridian. The integrated dawn-to-dusk electric field in the solar wind (Ey) showed a good correlation with |min. Dst| of the storms and the peak Ey (Eyp) and the peak southward interplanetary magnetic field showed next good correlations with |min. Dst|. We obtained the Eyp of 236 mV/m for |min. Dst| of 2500 nT of the expected upper limit of Earth’s magnetosphere using the empirical equations from the correlations between |min. Dst| and solar wind parameters and showed that this value of Ey is possible according to the past observations. The Eyp of 54 mV/m for the 13 March 1989 storm and that of 165/79 mV/m for the Carrington storm (|min. Dst|= 1760/850 nT) were also obtained. The analysis using the complimentary cumulative distribution function suggested the probabilities of Ey of 100, 200, 250, and 340 mV/m over the next 100 years to be 0.563, 0.110, 0.060 and 0.026, respectively.

Graphical Abstract
Factors influencing the bone mineral density in Duroc boars
Authors: Hu Lingling , Lu Jinxin , Guo Liangliang , Tan Jiajian , Sun Haiqing , Zhou Yuanfei , Wu Yinghui , Wei Hongkui , Jiang Siwen , Peng Jian
Published: May 2023

Background

Leg weakness affects animal welfare and is one of the primary reasons for culling of boars. Low bone mineral density (BMD) is one of the primary factors contributing to leg weakness. Low BMD also appeared to be associated with severe bone pain and has the highest risk of skeletal fragility. Surprisingly, few studies have been performed on the factors influencing BMD in pigs. Therefore, the primary aim of this study was to identify the influencing factors on boar BMD. Herein, the BMD data were determined through the use of ultrasonography from 893 Duroc boars. Logistic regression model was utilized in the analysis of BMD, in which the explanatory variables in the model were lines, ages, body weights, backfat thicknesses and serum mineral element concentrations (Ca, P, Mg, Cu, Fe, Zn, Mn, Se, Pb and Cd).

Results

Results showed that factors significantly influencing BMD included serum Ca, P concentrations, ages and backfat thicknesses (P < 0.05), in which serum Ca concentrations were positively correlated with BMD (P < 0.01), whereas increasing concentrations of serum P decreased BMD (P < 0.01). The serum Ca/P ratio showed significant quadratic effects on BMD (r = 0.28, P < 0.01), and the Ca/P ratio to achieve the best BMD was determined to be 3.7. Furthermore, BMD also changed with age quadratically (r = 0.40, P < 0.01), and reached a peak value around 47 months. Interestingly, a quadratic (r = 0.26, P < 0.01) increase in the BMD was observed as backfat thickness increased, and the inflection point was calculated at around 17 mm.

Conclusion

In conclusion, BMD characteristics of boars could be detected by ultrasonic method, and serum Ca, serum P, age, and backfat thickness contributed to the greatest effect on BMD.
Can infant carrier hip belts of 2-inch, 4-inch, and 6-inch dimensions influence trunk muscle activities during front infant carrying tasks?
Authors: Ojukwu Chidiebele Petronilla , Omeanu Clinton Ikechukwu , Nwosu Ifeoma Blessing , Ede Stephen Sunday , Aiyegbusi Ibifubara Ayoola , Anyaene Chiamaka Chinyere , Ikele Ikenna Theophilus
Published: May 2023

Background

Utilization of infant carriers (ICs) for childcare activities is common and involves varieties of hip belts to offer maximum maternal and infant support. There is a need to establish ergonomic-based guidelines for IC components as a means of improving their supportive roles.

Objective

This study evaluated the effects of infant carrier (IC) hip-belt dimensions on the erector spinae (ES) and multifidus (MF) muscles of healthy adult women during front infant carrying tasks.

Methods

It utilized three hip belts with different width dimensions (2 inch, 4 inch, and 6 inch) attached to the IC during three front infant carrying tasks, respectively. During each 5-min trial, the activities of the right and left components of the ES and MF muscles were simultaneously monitored via surface electromyography (EMG). Asymmetry ratios of the normalized EMG values of the right and left components of each muscle were calculated.

Results

Utilization of different hip-belt dimensions did not elicit significant (p < 0.05) differences in the electrical activities of the back muscles as well as in their asymmetry ratios. However, marginal differences in the normalized EMG values showed that the 4-inch belt elicited the highest muscular activities in three of the four studied muscles.

Conclusion

During simulated front infant carrying tasks, hip-belt dimensions of the ICs did not influence back muscle activities in healthy adult women. Long-term effects of IC hip-belt dimensions on back muscle activities should be evaluated in future studies.
Predicting future onset of depression among middle-aged adults with no psychiatric history
Authors: Bilu Yonatan , Kalkstein Nir , Gilboa-Schechtman Eva , Akiva Pinchas , Zalsman Gil , Itzhaky Liat , Atzil-Slonim Dana
Published: May 2023

Background

Depression is a major cause of disability worldwide. Recent data suggest that, in industrialised countries, the prevalence of depression peaks in middle age. Identifying factors predictive of future depressive episodes is crucial for developing prevention strategies for this age group.

Aims

We aimed to identify future depression in middle-aged adults with no previous psychiatric history.

Method

To predict a diagnosis of depression 1 year or more following a comprehensive baseline assessment, we used a data-driven, machine-learning methodology. Our data-set was the UK Biobank of middle-aged participants (N = 245 036) with no psychiatric history.

Results

Overall, 2.18% of the study population developed a depressive episode at least 1 year following baseline. Basing predictions on a single mental health questionnaire led to an area under the curve of the receiver operating characteristic of 0.66, and a predictive model leveraging the combined results of 100 UK Biobank questionnaires and measurements improved this to 0.79. Our findings were robust to demographic variations (place of birth, gender) and variations in methods of depression assessment. Thus, machine-learning-based models best predict diagnoses of depression when allowing the inclusion of multiple features.

Conclusions

Machine-learning approaches show potential for being beneficial for the identification of clinically relevant predictors of depression. Specifically, we can identify, with moderate success, people with no recorded psychiatric history as at risk for depression by using a relatively small number of features. More work is required to improve these models and evaluate their cost-effectiveness before integrating them into the clinical workflow.
The Feasibility, Acceptability, and Effectiveness of Electronic Patient-Reported Outcome Symptom Monitoring for Immune Checkpoint Inhibitor Toxicities: A Systematic Review
Authors: Lai-Kwon Julia , Cohen Jordan E. , Lisy Karolina , Rutherford Claudia , Girgis Afaf , Basch Ethan , Jefford Michael
Published: May 2023

PURPOSE

Increasing use of immune checkpoint inhibitors (ICIs) in routine cancer care will increase the incidence of immune-related adverse events (irAEs). Systems are needed to support remote monitoring for irAEs. Electronic patient-reported outcome (ePRO) symptom monitoring systems can help monitor and manage symptoms and side effects. We assessed the content and features of ePRO symptom monitoring systems for irAEs, and their feasibility, acceptability, and impact on patient outcomes and health care utilization.

METHODS

A systematic literature search was conducted in May 2022 on MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials. Quantitative and qualitative data relevant to the review questions were extracted and synthesized in tables.

RESULTS

Seven papers describing five ePRO systems were included. All systems collected PROs between clinic visits. Two of five used validated symptom questionnaires, 3/5 provided prompts to complete questionnaires, 4/5 provided reminders to self-report, and 3/5 provided clinician alerts for severe/worsening side effects. Four of five provided coverage of ≥26/30 irAEs in the ASCO irAE guideline. Feasibility and acceptability were demonstrated with consent rates of 54%-100%, 17%-27% of questionnaires generating alerts, and adherence rates of 74%-75%. One paper showed a reduction in grade 3-4 irAEs, treatment discontinuation, clinic visit duration, and emergency department presentations, while another showed no difference in these outcomes or the rate of steroid use.

CONCLUSION

There is preliminary evidence of the feasibility and acceptability of ePRO symptom monitoring for irAEs. However, further studies are needed to confirm the impact on ICI-specific outcomes, such as the frequency of grade 3-4 irAEs and duration of immunosuppression. Suggestions for the content and features of future ePRO systems for irAEs are provided.
Patient-Centered Care in the Management of Cancer During Pregnancy
Authors: Sorouri Kimia , Loren Alison W. , Amant Frédéric , Partridge Ann H.
Published: May 2023

The management of cancer during pregnancy requires a patient-centered, multidisciplinary approach to balance maternal and fetal well-being given the rarity of this clinical scenario and lack of substantial data. Involvement of oncology and nononcology medical specialists and ethical, legal, and psychosocial supports, as needed, is instrumental in navigating the complexities of care for this patient population. Critical periods of fetal development and physiological changes in pregnancy must be considered when planning diagnostic and therapeutic approaches during pregnancy. The complexity of symptom recognition and interventional approaches contributes to diagnostic delays of cancers during pregnancy. Ultrasound and whole-body diffusion-weighted magnetic resonance imaging are safe throughout pregnancy. Surgery can be safely performed throughout pregnancy, with the early second trimester preferred for intra-abdominal surgery. Chemotherapy can be safely administered after 12-14 weeks of gestation until 1-3 weeks before the anticipated delivery. Most targeted and immunotherapeutic agents are contraindicated during pregnancy because of limited data. Pelvic radiation during pregnancy is absolutely contraindicated, while if radiation to the upper body is needed, administration should only be considered early in pregnancy. To ensure that the total cumulative fetal exposure to ionizing radiation does not exceed 100 mGy, early inclusion of the radiology team in the care plan is required. Closer prenatal monitoring is recommended for maternal and fetal treatment-related toxicities. Delivery before 37 weeks of gestation should be avoided if possible, and vaginal delivery is preferred unless obstetrically indicated or specific clinical scenarios. Postpartum, breastfeeding should be discussed, and the neonate should receive blood work to assess for acute toxicities with follow-up arranged for long-term monitoring.
Treatment Decisions for Resectable Non–Small-Cell Lung Cancer: Balancing Less With More?
Authors: O'Reilly David , Botticella Angela , Barry Simon , Cotter Seamus , Donington Jessica S. , Le Pechoux Cecile , Naidoo Jarushka
Published: May 2023

For patients with non–small-cell lung cancer (NSCLC), the outcomes for patients with resectable disease are historically poor compared with other solid organ malignancies. In recent years, there have been significant advances in multidisciplinary care, which have resulted in improved outcomes. Innovations in surgical oncology include the use of limited resection and minimally invasive techniques. Recent data in radiation oncology have suggested refinements in pre- and postoperative radiation therapy, resulting in optimization of techniques in the curative setting. Finally, the success of immune checkpoint inhibitors and targeted therapies in the advanced setting has paved the way for inclusion in the adjuvant and neoadjuvant settings, resulting in recent regulatory approvals for four regimens (CheckMate-816, IMpower010, PEARLS, ADAURA). In this review, we will provide an overview of the seminal studies informing advancements in optimal surgical resection, radiation treatment, and systemic therapy for resectable NSCLC. We will summarize the key data on survival outcomes, biomarker analyses, and future directions for perioperative studies.
Radiofrequency Ablation of Unifocal Papillary Thyroid Microcarcinoma With BRAF V600E Mutation
Authors: Lin Yan , Wu Zhao-rong , Shi Yao-ping , Ding Min , Tang Xiao-yin , He Yi , Zhai Bo , Li Ping
Published: May 2023

Context

To date there is no study on the feasibility of radiofrequency ablation (RFA) for papillary thyroid microcarcinomas (PTMCs) with BRAF V600E mutation.

Objective

This study was designed to evaluate the efficiency, safety, and prognosis of ultrasound (US)-guided percutaneous RFA for unifocal PTMCs with BRAF V600E mutation.

Materials and Methods

Sixty patients with 60 unifocal BRAF V600E mutation–positive PTMCs who received US-guided RFA between January 2020 and December 2021 were retrospectively analyzed. The mean maximum PTMC tumor diameter was 5.8 ± 1.7 mm (range, 2.5-10.0 mm). All PTMCs were pathologically confirmed by fine needle aspiration or core needle biopsy, and BRAF V600E mutation was confirmed to be positive by real-time fluorescent quantitative polymerase chain reaction. Contrast-enhanced ultrasound (CEUS) was performed immediately after RFA to evaluate whether PTMCs were extendedly ablated. Ultrasound was performed 1, 3, 6, and 12 months after RFA and every 6 months thereafter to evaluate the changes in the ablation zone, local recurrence, and cervical lymph node metastasis (LNM). The complications were recorded and evaluated.

Results

Extended ablation was achieved in all enrolled patients. The ablation zone sizes increased immediately after RFA compared with those of tumors before treatment. One month later, the ablation zone sizes were smaller than immediately after RFA. At the last follow-up assessment, 42 nodules (70.0%) completely disappeared and the ablation zones of 18 nodules (30.0%) showed fissure-like changes. No local recurrence or cervical LNM was detected. Voice change (1.7%) was the only major complication.

Conclusion

RFA is effective and safe in treating unifocal PTMCs with BRAF V600E mutation, especially when surgery is not feasible or refused by patients who are unwilling to continue active surveillance.
Time to Recurrence as a Prognostic Factor in Parathyroid Carcinoma
Authors: Magnabosco Felipe Ferraz , Brescia Marilia D’Elboux Guimarães , Nascimento Júnior Climério Pereira , Massoni Neto Ledo Mazzei , Arap Sergio Samir , de Castro Junior Gilberto , Ledesma Felipe Lourenço , Ferreira Alves Venancio Avancini , Kowalski Luiz Paulo , Martin Regina Matsunaga , de Menezes Montenegro Fabio Luiz
Published: May 2023

Background

Parathyroid carcinoma (PC) is a rare and challenging disease without clearly understood prognostic factors. Adequate management can improve outcomes. Characteristics of patients treated for PC over time and factors affecting prognosis were analyzed.

Methods

Retrospective cohort study including surgically treated patients for PC between 2000 and 2021. If malignancy was suspected, free-margin resection was performed. Demographic, clinical, laboratory, surgical, pathological, and follow-up characteristics were assessed.

Results

Seventeen patients were included. Mean tumor size was 32.5 mm, with 64.7% staged as pT1/pT2. None had lymph node involvement at admission, and 2 had distant metastases. Parathyroidectomy with ipsilateral thyroidectomy was performed in 82.2%. Mean postoperative calcium levels were different between patients who developed recurrence vs those who did not (P = .03). Six patients (40%) had no recurrence during follow-up, 2 (13.3%) only regional, 3 (20%) only distant, and 4 (26.6%) both regional and distant. At 5 and 10 years, 79% and 56% of patients were alive, respectively. Median disease-free survival was 70 months. Neither Tumor, Nodule, Metastasis system nor largest tumor dimension (P = .29 and P = .74, respectively) were predictive of death. En bloc resection was not superior to other surgical modalities (P = .97). Time between initial treatment and development of recurrence negatively impacted overall survival rate at 36 months (P = .01).

Conclusion

Patients with PC can survive for decades and have indolent disease course. Free margins seem to be the most important factor in initial surgery. Recurrence was common (60%), but patients with disease recurrence within 36 months of initial surgery had a lower survival rate.
Inhibitory SMAD6 interferes with BMP dependent generation of muscle progenitor cells and perturbs proximodistal pattern of murine limb muscles
Authors: Asfour Hasan , Hirsinger Estelle , Rouco Raquel , Zarrouki Faouzi , Hayashi Shinichiro , Swist Sandra , Braun Thomas , Patel Ketan , Relaix Frédéric , Andrey Guillaume , Stricker Sigmar , Duprez Delphine , Stantzou Amalia , Amthor Helge
Published: May 2023

The mechanism of pattern formation during limb muscle development remains poorly understood. The canonical view holds that naïve limb muscle progenitor cells (MPCs) invade a pre-established pattern of muscle connective tissue, thereby forming individual muscles.

Here we show that early murine embryonic limb MPCs highly accumulate pSMAD1/5/9, demonstrating active signaling of bone morphogenetic proteins (BMP) in these cells. Overexpression of inhibitory SMAD6 in limb MPCs abrogated BMP signaling, impaired their migration and proliferation, and accelerated myogenic lineage progression. Fewer primary myofibers developed, causing an aberrant proximodistal muscle pattern. Patterning was not disturbed when SMAD6 was overexpressed in differentiated muscle, implying that the proximodistal muscle pattern depends on BMP-mediated expansion of MPCs prior to their differentiation. We show that limb MPCs differentially express Hox genes, and Hox-expressing MPCs displayed active BMP signaling. SMAD6 overexpression caused loss of HOXA11 in early limb MPCs. In conclusion, our data show that BMP signaling controls expansion of embryonic limb MPC as a prerequisite for establishing the proximodistal muscle pattern, a process that involves expression of Hox genes.
The bHLH-PAS transcriptional complex Sim:Tgo plays active roles in late oogenesis to promote follicle maturation and ovulation
Authors: Oramas Rebecca , Knapp Elizabeth M , Zeng Baosheng , Sun Jianjun
Published: May 2023

Across species, ovulation is a process induced by a myriad of signaling cascades that ultimately leads to the release of encapsulated oocytes from follicles. Follicles first need to mature and gain ovulatory competency before ovulation; however, the signaling pathways regulating follicle maturation are incompletely understood in Drosophila and other species. Our previous work has shown that the bHLH-PAS transcription factor Single-minded (Sim) plays important roles in follicle maturation downstream of the nuclear receptor Ftz-f1 in Drosophila. Here, we demonstrate that Tango (Tgo), another bHLH-PAS protein, acts as a co-factor of Sim to promote follicle cell differentiation from stages 10 to 12. In addition, we discover that re-upregulation of Sim in stage-14 follicle cells is also essential to promote ovulatory competency by upregulating octopamine receptor in mushroom body (OAMB), matrix metalloproteinase 2 (Mmp2) and NADPH oxidase (NOX), either independently of or in conjunction with the zinc-finger protein Hindsight (Hnt). All these factors are crucial for successful ovulation. Together, our work indicates that the transcriptional complex Sim:Tgo plays multiple roles in late-stage follicle cells to promote follicle maturation and ovulation.
PATL2 regulates mRNA homeostasis in oocytes by interacting with EIF4E and CPEB1
Authors: Zhang Zhihua , Liu Ruyi , Zhou Hongbin , Li Qun , Qu Ronggui , Wang Weijie , Zhou Zhou , Yu Ran , Zeng Yang , Mu Jian , Chen Biaobang , Guo Xuejiang , Sang Qing , Wang Lei
Published: May 2023

The accumulation and storage of maternal mRNA is crucial for oocyte maturation and embryonic development. PATL2 is an oocyte-specific RNA-binding protein, and previous studies have confirmed that PATL2 mutation in humans and knockout mice cause oocyte maturation arrest or embryonic development arrest, respectively. However, the physiological function of PATL2 in the process of oocyte maturation and embryonic development is largely unknown. Here, we report that PATL2 is highly expressed in growing oocytes and couples with EIF4E and CPEB1 to regulate maternal mRNA expression in immature oocytes. The germinal vesicle oocytes from Patl2−/− mice exhibit decreasing maternal mRNA expression and reduced levels of protein synthesis. We further confirmed that PATL2 phosphorylation occurs in the oocyte maturation process and identified the S279 phosphorylation site using phosphoproteomics. We found that the S279D mutation decreased the protein level of PATL2 and led to subfertility in Palt2S279D knock-in mice. Our work reveals the previously unrecognized role of PATL2 in regulating the maternal transcriptome and shows that phosphorylation of PATL2 leads to the regulation of PATL2 protein levels via ubiquitin-mediated proteasomal degradation in oocytes.
Debt Distress on China’s Belt and Road
Authors: Horn Sebastian , Parks Bradley C. , Reinhart Carmen M. , Trebesch Christoph
Published: May 2023

This paper shows that China's lending boom to developing country sovereigns has largely ended and that debt distress and defaults are increasingly common. Chinese lenders react to this challenge through two main coping strategies: first, bilateral sovereign debt restructurings–typically with maturity extensions but no face value cuts–and, second, rescue loans that allow debtors to avoid or delay default. Low-income countries tend to receive debt restructurings, whereas emerging market countries are more likely to receive rescue loans. We speculate that the differential crisis response is due to the different exposure levels of Chinese state banks.
Learning Curve: Progress in the Replication Crisis
Authors: Angrist Noam , Cullen Claire , Ainomugisha Micheal , Bathena Sai Pramod , Bergman Peter , Crossley Colin , Letsomo Thato , Matsheng Moitshepi , Panti Rene Marlon , Sabarwal Shwetlena , Sullivan Tim
Published: May 2023

We present detailed monitoring data across a five-country randomized trial of phone-based targeted tutoring–one of the largest multicountry replication efforts in education to date. We study an approach shown to work in Botswana and replicated in India, Kenya, Nepal, the Philippines, and Uganda. While the existing literature often finds diminishing effects as proof-of-concept studies are replicated and scaled, we find the opposite: implementation fidelity (the degree of targeted educational instruction) improves across replications and over time. This demonstrates that replication is not intractable; rather, equipped with mechanisms to learn from experience, organizational “learning curves” can enable effective replication and scale-up.
Exacerbated Inequalities: The Learning Loss from COVID-19 in Italy
Authors: Carlana Michela , La Ferrara Eliana , Lopez Carolina
Published: May 2023

Using administrative data on the universe of eighth graders, we study learning losses in Italy between 2021 and 2019 to estimate the effect of schools' closures due to the COVID-19 pandemic. We find an average learning loss of 0.14 SD in math and 0.05 SD in reading. The pandemic widened preexisting gaps by socioeconomic status (SES): students in the bottom quintile of SES learned 0.21 SD less in math and 0.10 SD less in reading. Learning losses for immigrant students in math are larger than those for native ones. We do not find economically significant differences by gender.