bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Anti-Epileptic Drugs Usage on Thyroid Profile in Egyptian Epileptic Children
Authors: Kirolos Bichara Amira Rafik , Abou Shady Eman Moenes , Mohamed Ali Nada Maha Ali , El Khayat Naglaa Mohamed , El-Din Ahmed Nahed Salah
Published: July 2024

Background

AEDs Has been associated with disturbances in thyroid functions. This was studied in adults but there is contradictory data in children especiall newer AEDs.

Objective

This study aims to compare the effects of conventional and newer AEDs whether mono or polytherapy on thyroid profile in epileptic children.

Results

This study included 155 children with epilepsy (54.84 % euthyroid, 31.61% hypothyroid, 9.68% subclinical hypothyroid and 3.87 % subclinical hypothyroid) and 78 healthy controls. Epileptic children compliant on AEDS either mono-therapy or poly-therapy are associated with a statistically significant thyroid profile abnormalities (hypothyroidism, sub-clinical hypothyroidism or sub-clinical hyperthyroidism). There was no statistically significant difference between poly-therapy and mono-therapy. Carbamazepine had a statistically significant association with hypothyroidism and valproic acid had a statistically significant association with sub-clinical hypothyroidism. LEV also wa associated with significat thyroid dysfunction. There was no statistically significant difference between those on two AEDS those on three AEDS and those on four or five AEDS.

Conclusion

AEDs whether older or newer generations can effect thyroid profile. Anti –epileptic drugs whether conventional or new ones are associated with hypothyroidism, sub-clinical hypothyroidism, sub- clinical hyperthyroidism.
The Correlation between Body Mass Index and Intraocular pressure, Retinal Nerve Fiber Layer Thickness and Visual Field
Authors: Hassan Rana M , El-Shazly Amany Abd El-Fattah , Farweez Yousra A , Karim Marwa A
Published: July 2024

Background

Obesity has become a world-wide medical epidemic. it constitutes an important risk for several eye diseases like cataract, diabetic retinopathy, age related macular degeneration (AMD) and glaucoma.Body mass index (BMI) is one of the most specific and objective measurement to define obesity. Obesity has recently been reported to be negatively associated with visual acuity, but the ocular conditions underlying this association and the potential implications are unclear. Amongst different eye diseases, obesity has been associated with cataract, age-related maculopathy, diabetic retinopathy, and glaucoma.

Purpose

To investigate the relationship between BMI and IOP and correlate it with changes in RNFL thickness and visual field.

Materials and Methods

60 participants divided into three groups (normal, overweight, and obese) according to BMI, were included in this Cross-Sectional Study (pilot study). Participants underwent a complete ophthalmologic assessment, measurement of RNFL thickness and ganglion cell complex (GCC) thickness using SD-OCT, IOP with Goldmann applanation tonometry (GAT) and visual field analysis using Humphrey field analyser.

Results

IOP was significantly higher in obese group than those in healthy weight and overweight group. Also, IOP was statistically significant higher in overweight group compared with those healthy weight group. There were no significant differences between the three groups in average, superior, inferior, nasal, and temporal RNFL thicknesses or in GCC thickness. Yet, GCC thickness in the obese group showed significant negative correlation with BMI.There were no significant differences between the three groups in MD, and VFI.

Conclusion

IOP was variable according to the degree of obesity with incremental pattern with advance of BMI. BMI of overweight group had no correlation with IOP, average, superior, inferior, nasal, and temporal RNFL thicknesses. While BMI of obese group showed a significant positive correlation with IOP and negative correlation with GCC thickness.
Outcome of Neonatal Registry Through Electronic Medical Registry at Neonatal Intensive Care Units, Children's Hospital of Ain Shams University
Authors: El-Farrash Rania Ali , Mohamed Ammar Alaa Ragab , Farid Yasmin A
Published: July 2024

Background

The neonatal mortality rate is 19 deaths per 1000 live births worldwide. Studies have shown that neonatal registry network systems can provide the necessary data for establishing evidence- based strategies to decrease the complications in high-risk neonates and consequently reduce neonatal mortality rate.

Aim of the Work

To determine the frequency and distribution of neonatal critical illnesses in Neonatal Intensive Care Unit (NICU) of Ain Shams University.

Patients and Methods

This descriptive study was conducted in NICU, Children's Hospital, Ain Shams University. The data collected from initiated neonatal registry through electronic medical record to reach sample size number (381) patients. The current study was conducted after approval by the Department of Pediatrics, and the local Ethics and Research Committee, Faculty of Medicine, Ain Shams University.

Results

The mean ± (SD) age at admission was 5.52 ± 6.9 days, gestational age was 36.19 ± 2.47 weeks, more than half of our patients were males (55.6%) and females represented in (44.4%). Two- thirds (64.2%) of our participants were full term, and preterm were only (35.7%). The main etiology of NICU admission was respiratory disease (35.7%), followed by neonatal sepsis (25.2%), neonatal jaundice (21%), congenital anomalies (12.3%), CNS diseases (6.8%), inborn errors of metabolism (1%) and mortality rate was 10.5%. Four cases had inborn errors of metabolism in the form of: Maple syrup urine disease (one case), organic academia (one cases) and 2 cases referred to genetic clinic for further assessment. Congenital heart diseases in our study was reported in (7.9%) of neonates. The main etiology among them was reported in following order: PDA / pulmonary hypertension (26.7%), VSD (13.3%), Fallot tetralogy (10%), transposition of great arteries (10%), supraventricular tachycardia (6.7%) then many etiologies represented in 3.3% as Ebstein anomaly, right single ventricle, heart block, pulmonary artery stenosis, arrhythmia, tricuspid atresia and left hypoplastic heart disease.

Conclusion

This study showed the ability of the electronic medical record to store large amounts of data which creates a potential for information overload in the intensive care (ICU) setting. This will stimulate and facilitate research on neonatal critical illness and its management, mortality and morbidity outcomes of neonates admitted to NICUs in Children's Hospital, Ain Shams University, Egypt.
Screening of Palatopharyngeal Incoordination in Mechanically Ventilated Critically Ill Infants
Authors: Ibrahim Youssef Hanan M , Rezk Ahmed R , Abdel Hameed Mohamed Abeer Maghawry , Refaat Salem Ahmed Mohamed , Ahmed Mohamed Ahmed Elsayed
Published: July 2024

Background

Palatopharyngeal incoordination is a common phenomenon in patients requiring endotracheal intubation for mechanical ventilation. Understanding the underlying mechanism of palatopharyngeal incoordination may help as a screening tool that improves rates of early recognition and diagnosis and the ability to take preventive measures essential to alleviate related morbidity and complications.

Objective

The aim of this study is to screen palatopharyngeal incoordination in infants who needed mechanical ventilation and to elicit palatopharyngeal incoordination secondary to mechanical ventilation.

Material and Methods

This study included 51 patients at the Pediatric Intensive Care Unit, Faculty of Medicine, Ain Shams University, The study was conducted during the period from February 2021 to February 2022. patients were classified according to a Fiberoptic Flexible Endoscopic Evaluation of Swallowing (FEES) early post intubation, FEES early post extubation, Videofluoroscopic Swallow Study (VFSS) post extubation and dye study into five groups: group (1) the not affected group, group (2) the palatopharyngeal incoordination group, group (3) The palatopharyngeal incoordination with gastro esophageal reflux group, group (4) The reflux group, group (5) The congenital upper air way anomalies group in which patients were ventilated due to respiratory distress. Follow up FEES and VFSS were done after three months for palatopharyngeal incoordination patients.

Results

Palatopharyngeal incoordination was detected in 16 patients (31.3%), congenital upper airway anomalies were found in 12 patients (23.5%), and gastroesophageal reflux was only detected in 10 patients (19.6%). Performing VFSS and FEES after three months showed 92.3 % of palatopharyngeal incoordination patients had resolved palatopharyngeal incoordination and 7.7 % of palatopharyngeal incoordination patients had silent aspiration.

Conclusion

The prevalence of palatopharyngeal incoordination is 31.3 % and there was no palatopharyngeal incoordination secondary to mechanical ventilation.
Lung Ultrasound Evaluation of Pulmonary Abnormalities in Children with Congenital Heart Diseases
Authors: Elsayed Eman Mohamed , Elguindy Waleed Mohamed , Ahmed Farag Amina Mohamed , Ahmed Ali Esraa Ibrahim , Hussein Mahitab Morsy
Published: July 2024

Background and Aims

Congenital heart disease (CHD) can cause several abnormalities of the lungs, such as pulmonary overflow (PO), pulmonary hypertension and chest infection like pneumonia. We aimed to assess pulmonary abnormalities using lung ultrasound (LUS) in children with congenital heart diseases.

Patients and Methods

This is a cross-sectional study, which included (33) CHD patients aged between 0.5 to 3.5 years who were admitted to the Cardiology Unit,Ain Shams University, Children’s Hospital. The patients were subjected to detecting any consolidation and measuring B vertical lines in all lung zones. LUS score was recorded at baseline and after course of management.

Results

There was statistically reduction in the after management group compared to the before management group according to LUS score with p-value (p < 0.001). There was a difference between types of management according to LUS score and its severity in the before management group, with p-value (p < 0.001) whereas, surgical type of management had the highest mean value of the LUS score compared to other types of management among our studied patients before management with a highly statistically significant difference, with p-value (p < 0.001).

Conclusion

Lung ultrasound is an ideal tool for the diagnosis and follow-up of pulmonary complications such as lung congestion, pulmonary edema and pneumonia. Also, there was improvement in pulmonary congestion after management among CHD children.
Spinal Cord Involvement in Children with Acquired Demyelinating Syndromes: A Single Centre Study
Authors: El-Agouza Iman Ali , Ahmed Khaled Aboulfotouh , Ahmed Abualwafa Sarah Tarek Abdelsamie , Hesham Zaitoun Raghda Mohamed
Published: July 2024

Background

Myelitis may be the first presentation of relapsing acquired demyelinating syndromes (ADS) such as neuromyelitis optica (NMO) or multiple sclerosis (MS) and in association with connective tissue diseases. It may also occur in the context of acute disseminated encephalomyelitis (ADEM). Early recognition of myelitis in these disorders will allow better management plan including theprognosis.

Objective

To evaluate the frequency of myelitis among children with acquired demyelinating neurological diseases, and the variability of clinical features, neuroimaging findings and treatments given.

Methods

A pilot observational study with both retrospective and prospective components was conducted on children and adolescents fulfilling the diagnostic criteria for any of the acquired demyelination syndromes admitted inChildren’s Hospital, Ain Shams University whose ages were below 18 years during the period from July 2020 to February 2022.

Results

Forty-three children were included in our study with mean (SD)age of onset 7.63 (4.28) years. The most common diagnosis was ADEM (n (%) =20 (46.5%), followed by transverse myelitis (TM) (n (%) =11 (25.6%) and NMO (n (%) =7(16.3%). Progression to develop encephalopathy was recorded in 55.8%of cases (100% of ADEM and autoimmune encephalitis (AE) cases). Seizures developed in 23.3% of cases (35% of ADEM, 50% of AE and 14.29% of NMO cases). MRI brain abnormalities were observed in 76.7% of cases (100% of ADEM, NMO, AE and MS cases), and abnormalities of MRI spine were seen in 59% of cases (100% of TM and MS cases, 85.7% of NMO, 33.3% of AE and 23.5% of ADEM cases). Spinal cord affection was most commonly cervical(86.9%) and mostly short segment. All cases received pulsed methylprednisolone therapy, while intravenous immunoglobulins (IVIG) were used in 32.5% of cases and plasmapheresis in 13.9% of cases as a stepwise approach. Nearly half of the cases (53.5%) had monophasic illnesses without the need for long term therapy.

Conclusion

Spinal cord involvement is frequently observed in childhood acute demyelinating syndromes, and is most commonly cervical and short-segment. MRI spine should be regarded as a sensitive tool for diagnosis of myelitis in the context of ADEM and MS. MRI Brain is a sensitive tool accounting forfindings in 100% of ADEM, NMO, AE and MS cases. Patients with ADEM and AE has higher risk to develop encephalopathy and seizures unlike TM, NMO and MS patients.
Hypertrophic Cardiomyopathy Risk Factors in Infants of diabetic mothers
Authors: Abou Shady Nancy Mohamed , Azzam Nesmahar Tarek , Atef Alaa Mohamed , Atia Abdelmaksoud Eman Abdelmaksoud
Published: July 2024

Background

Diabetes mellitus (DM) is a systemic chronic metabolic disorder characterized by increased insulin resistance and/or β- cell defects. Maternal DM significantly affects the fetal heart and fetal–placental circulation in both structure and function. Cardiac defects, myocardial hypertrophy are three times more prevalent in infants of diabetic mothers (IDMs).

Objective

Assess the frequency of hypertrophic cardiomyopathy (HCM) among infants of diabetic mothers and its relationship to the maternal glycemic control and the birth weight for the gestational age.

Patients and Methods

This was a cross-sectional study conducted on (50) neonates with gestational age ≥ 35 weeks born to diabetic mothers recruited from the delivery room and Neonatal Observation Unit, Obstetrics and Gynecology Hospital, Ain shams university. Detailed history was taken for the duration of maternal diabetes, glycemic control and any associated complications and the level of hemoglobin A1C (HbA1C) was assessed for all the enrolled mothers. Neonates were subjected to full clinical examination and echocardiographic evaluation in the first week of life.

Results

Forty % of mothers had gestational diabetes mellitus (GDM), (20%) were pre-gestational diabetes type 1 and 40% were pre-GDM type 2. There were 18 infants (36%) had HCM. HCM was highly statistically significant (p-value < 0.001) more in cases with high maternal HbA1C (8.3 ± 0.9). The frequency of HCM among infants of pre-GDM mothers (15 patients, 50%) was significantly higher (p-value = 0.012) when compared to infants of GDM mothers (3 patients, 15%). But the frequency of HCM was equal in infants of pre-GDM type I mothers and those of pre-GDM type 2 mothers. HCM was more common with large for gestational age (LGA) infants (10 cases 55.6% of infants with HCM were LGA).

Conclusion

HCM is more frequent among infants of mothers with pre-GDM type 1 than infants of GDM. Poor maternal glycemic control and large for gestational age are associated with higher frequency of HCM among those infants.
Epidemiology of Household Transmission of COVID-19 among Patients Attending Outpatient Clinics of Teaching Hospital in Cairo, Egypt
Authors: Ali Dalia F , Abozaid Dena A , Elbagoury Lamyaa S , Abd Elaziz Khaled M
Published: July 2024

Background

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). People in closed settings with COVID-19 patients, such as household contacts, were more likely to become infected. Household studies can provide informative data for COVID-19 prevention and control.

Aim

to identify the epidemiological features of household transmission in a sample of patients attending the family medicine clinic of a tertiary hospital in Egypt, and to calculate the household COVID19 secondary clinical attack rate for the recruited patients.

Materials and Methods

An observational follow-up study was conducted among a sample of 180 primary probable COVID-19 cases attending a tertiary hospital in Cairo, Egypt and their 395 household contacts. The modified WHO case reporting form was used for follow-up of primary probable COVID-19 cases, and the modified WHO contact reporting form was used for their household contacts follow-up. Follow-up phone calls were conducted after 7, 10, and 14 days after attending to the hospital.

Results

The mean household Secondary clinical attack rate is 65.3 ± 29.9 (95 CI: 60.5% - 70.1%). There was a significant statistical association between reporting symptoms consistent with COVID-19 and sharing a room with the primary case, being not vaccinated, not using Personal protective equipment (PPE) as well as taking care of a primary case (p < 0.001).

Conclusion and Recommendations

Secondary clinical attack rate among the household contacts was high; more than the average reported rates globally. Vaccination and using PPE had important roles in lowering the risk of reporting symptoms consistent with COVID-19 among household contacts, yet the overall rate of using PPE was low and vaccination coverage was low compared to the rates reported globally. which necessitates more efforts to increase awareness of household transmission and how to safely care for a home-isolated COVID-19 case. The presence of co-morbidities increased the risk of hospitalization among symptomatic contacts This gives an alert to increase the awareness of cases with comorbidities about warning signs that necessitate early hospitalization for a better prognosis. about using PPE among household contacts with a COVID-19 case and also about the importance of vaccination against COVID- 19.
15 Years Survival of Budd-Chiari Patients in a Single Center Study
Authors: Zaki Helmy Ali Ahmed , Salem Hossam Mohamed , Elsayed Enaam Ali , Khalil Dabbous Ahmed Hesham
Published: July 2024

Background

Budd–Chiari syndrome (BCS) is a heterogeneous group of clinical conditions ranging from acute liver failure to completely asymptomatic patient. It is caused by hepatic venous outflow obstruction at any level from the small hepatic veins (HVs) to the junction of inferior vena cava (IVC) with the right atrium.

Aim of the Work: The idea of this work was to report the result so favast clinical experience over 15 years presented by Tropical medicine department Ain Shams University through analysing the patient and disease characteristics, outcome, complications and innovations in therapeutic intervention. Ultimately this should throw lights on the understanding of the pathophysiology causes and clinical consequences of BCS among Egyptian patients.

Patients and Methods

199 Egyptian patients with confirmed diagnoses of primary BCS were evaluated regarding their socio-demographic features, etiology, risk factors for BCS, clinical manifestations, management modalities and outcomes. The studied patients were enrolled from patients presented to Budd chiari study group clinic, Tropical Medicine Department ward, Ain Shams University hospitals, from January 2006 till December 2021.

Results

The commonest complaints in Budd Chiari patients were abdominal enlargement in 79.9% (159 patients) and abdominal pain in 77.9% (155 patients), Ascites was present in 75.4% (150), Hepatomegaly in 75.4% (150), Splenomegaly 61.8% (123). More than Seventy Seven percent (77.9%) of the enrolled patients were Chronic BCS patients, 12.6% were subacute BCS and 9.5% were acute BCS. In this study the leading cause of Budd-Chiari was FVLM 76 patients (38.2%). Several papers concluded that FVLM is the main or leading etiology to BCS but regarding the other papers that showed different results, these differences might possibly be due to the difference in sample size. In the current study the outcomes varied from one etiological factor to the other as in FVLM 78.7% of the BCS FVLM patients were compensated, 14.7% were decompensated and 6.7% died and these results were highly significant.

Conclusion

It seems that TIPS creation is an effective treatment for eligible BCS patients and has long-term survival benefit with satisfactory shunt patency and patient survival. The outcome of TIPS has improved over the years due to the increase in the operator experience and the availability of PTFE-covered stents.
Evaluation of a Rapid PSA Test for Prostate Cancer Screening
Authors: Mohamed Ali Ali Khaled , Elsaid Mohamed Hasan , Gad Hany Hamed
Published: July 2024

Background

Prostate-specific antigen (PSA) is a protein produced by normal prostate cells. This enzyme participates in the dissolution of the seminal fluid coagulum and plays an important role in fertility. The highest amounts of PSA are found in the seminal fluid; some PSA escapes the prostate and can be found in the serum.

Aim of the Work

to detemine accuracy, sensitivity, specificity of one-step PSA test (Fortel Test®) “FDA approved” for screening for prostate cancer in comparison to a conventional quantitative assay.

Patients and Methods

This Prospective cohort clinical study was conducted at tertiary care hospital at Urology Department, Outpatient clinic, Faculty of Medicine, Ain Shams University from January 2022 till June 2022 and performed on a total of 150 patients who were above 50 years old or above 40 years old with family history of prostate cancer.

Results

Our study results revealed that Fortel PSA test had high Sensitivity (97.2%), specificity (96.2%), positive predictive value (95.9%) and negative predictive value (97.4%) in accuracy of screening of prostatic cancer.

Conclusion

The Fortel PSA test is a simple, feasible, and reproducible tool for PC screening. The lower cost, ease of handling, and rapid procedure could make this test useful in the general practitioner or urologist office setting as well as for mass primary PC screening.
Evaluation of the Efficacy of Mini Percutaneous Nephrolithotomy in Comparison with Standard Percutaneous Nephrolithotomy for the Management of Large Renal Stones, a Randomized Controlled Clinical Trial
Authors: Osman Tarek , ElSaeed Karim Omar , Sadeq Mohammed Metwally
Published: July 2024

Background

Management of renal calculi targets complete clearance without any residual fragments, along with pain relief and eradication of the causative micro- organisms. Percutaneous nephrolithotomy (PNL) is currently the standard treatment option for patients with complex and large renal stones. However, innovations in instruments and techniques have resulted in “miniperc”, which was found to be safe and effective.

Aim and Objectives

to compare between mini PNL and the standard PNL in management of renal stones (20-40 mm) regarding operative time, fluoroscopy time, blood loss, stone free rate, and postoperative complications according to modified Clavein system.

Subjects and Methods

This prospective randomized comparative study was carried out at Urology department Ain Shams University hospitals, from 2019 to 2022 on 93 patients coming for renal stone management. Patients were divided into 2 groups: Group A included 44 patients who underwent standard PNL, whereas Group B included 49 patients who underwent mini PNL. Result The standard PNL yielded shorter operating time 70.1 ± 13.9 min vs 96.4 ±14.3 min,p <0.001) Patients in the standard PNL group also had longer hospitalization time, nephrostomy time and catheterization time(4 vs 3 days, 36 vs 24 hours and 5 vs 4 days respectively, p < 0.001). The mean drop in hemoglobin level that necessitated blood transfusion was significantly lower in the mini PNL group (0.7 vs 1.6 gm/dl, p < 0.0001). Although the stone-free rate was higher in the standard PNL group, but this was statistically insignificant (79.5 vs 61.2%, p = 0.054) According to modified Clavien–Dindo classification, no statistical difference was detected between the 2 groups in terms of complication rates The postoperative pain and the need for postoperative analgesia were significantly more in standard PNL patients. Visual Analogue Score (VAS) was 7.4 and 5.2 in standard PNL and mini PNL respectively.

Conclusion

We compared the standard PNL and mini PNL regarding the safety and efficacy in management of large renal stones. Standard PNL achieved higher stone free rate and shorter operative time while mini PNL has the advantage of shorter hospitalization time and low incidence of postoperative complications and pain.
Effect of JJ Stent on Outcomes of Extracorporeal Shockwave Lithotripsy of Renal Stones around 2 cm
Authors: El-Zayat Tarek Mostafa , Ahmed Tolba Mohamed Kotb , El-Said Soliman Mohamed Nabil
Published: July 2024

Background

Urolithiasis is a common problem in Egypt as it lies within the stone belt region extending from Indonesia to Egypt. Economic and dietary factors, dehydration, exposure to heat and possible genetic factors. Urolithiasis is one of the most common problems encountered by urologists. Many factors affect Stone formation like geographical, climatic, ethnic, dietary and genetic factors. The recurrence rate is determined by the primary etiology of stones formation.

Aim of the Work

Evaluation of the role of JJ stent in enhancing the passage of fragments in patients undergoing extracorporeal shockwave lithotripsy (ESWL) for renal stones with size around 2 cm.

Patients and Methods

This randomized controlled clinical trial was conducted on 90 patients in the period from December 2021 to July 2022 with age ranged from 24 – 60 years with mean±SD of 44.21 ± 10.99 years; they were 28 females (31.1%) and 62 males (68.9%) and randomly divided into two groups: Group (I): Patients without JJ stent consists of 45 patients & Group (II): Patients with JJ stent consists of 45 patients.

Results

The analysis of our study results showed no statically significant difference between the two groups regarding SFRs (95.6% in group I & 93.3% in group II), time to SFRs (mean±SD 1.05 ± 0.55 month in group I & 1.20 ± 0.59 month in group II), number of sessions of ESWL (2.11 for group I & 2.37 for group II), auxillary procedures (Two patients in group I (4.4%) 1 patient had PCNL & 1 patient had URS due to steinStrasse 2.2%) & Three patients in group II (6.7%) failed ESWL and had PCNL), number of ER visits (in group I 46.7% & in group II 40 % had attended at least once for the ER, analgesics consumption (In group I 77.8% & In group II 84.4%) & laboratory tests changes like Hb drob between pre & post ESWL in the two groups (-0.02 ± 0.04 & -0.11 ± 0.08 in group I & group II respectively) & the amount of increase in serum creatinine level (post – pre) was found 0.07 ± 0.03 in patients without JJ stent and 0.03 ± 0.04 in patient with JJ stent.

Conclusion

Routine JJ stent fixation before extracorporeal shock wave lithotripsy in management of renal stones around 2cm is unnecessary because it doesn’t improving free stone rate or enhancing the passage of the fragments during ESWL.
The chondrocyte “mechanome”: Activation of the mechanosensitive ion channels TRPV4 and PIEZO1 drives unique transcriptional signatures
Authors: Nims Robert , Palmer Daniel R. , Kassab Jordan , Zhang Bo , Guilak Farshid
Published: July 2024

The mechanosensitive ion channels Transient Receptor Potential Vanilloid 4 (TRPV4) and PIEZO1 transduce physiologic and supraphysiologic magnitudes of mechanical signals in the chondrocyte, respectively. TRPV4 activation promotes chondrogenesis, while PIEZO1 activation by supraphysiologic deformations drives cell death. The mechanisms by which activation of these channels discretely drives changes in gene expression to alter cell behavior remain to be determined. To date, no studies have contrasted the transcriptomic response to activation of these channels nor has any published data attempted to correlate these transcriptomes to alterations in cellular function. This study used RNA sequencing to comprehensively investigate the transcriptomes associated with activation of TRPV4 or PIEZO1, revealing that TRPV4 and PIEZO drive distinct transcriptomes and also exhibit unique co‐regulated clusters of genes. Notably, activation of PIEZO1 through supraphysiologic deformation induced a transient inflammatory profile that overlapped with the interleukin (IL)‐1‐responsive transcriptome and contained genes associated with cartilage degradation and osteoarthritis progression. However, both TRPV4 and PIEZO1 were also shown to elicit anabolic effects. PIEZO1 expression promoted a pro‐chondrogenic transcriptome under unloaded conditions, and daily treatment with PIEZO1 agonist Yoda1 significantly increased sulfated glycosaminoglycan deposition in vitro. These findings emphasize the presence of a broad “mechanome” with distinct effects of TRPV4 and PIEZO1 activation in chondrocytes, suggesting complex roles for PIEZO1 in both the physiologic and pathologic responses of chondrocytes. The identification of transcriptomic profiles unique to or shared by PIEZO1 and TRPV4 (distinct from IL‐1‐induced inflammation) could inform future therapeutic designs targeting these channels for the management and treatment of osteoarthritis.
Association Between Telecommuting Preference-Frequency Mismatch and Insomnia Among Japanese Workers in the COVID-19 Pandemic
Authors: Hamada Shinsuke , Okawara Makoto , Tateishi Seiichiro , Eguchi Hisashi , Tsuji Mayumi , Ogami Akira , Mori Koji , Matsuda Shinya , Yoshimura Reiji , Fujino Yoshihisa ,   for the CORoNaWork Project
Published: July 2024

Objective

We hypothesized that telecommuting's impact on sleep varied based on preference-frequency mismatch. Here, we evaluated this relationship in a large cohort of Japanese workers.

Methods

We collected data from 33,302 Japanese workers through an online survey and analyzed participant preferences and frequency of telecommuting in 9425 individuals who responded to a follow-up survey. We evaluated sleep using the Athens Insomnia Scale and estimated odds ratios of insomnia using multilevel logistic regression.

Results

Workers preferring telecommuting had a higher risk of insomnia as telecommuting frequency decreased. OR for insomnia was 1.87 (P < 0.001) in those who telecommuted less than once per week.

Conclusion

Telecommuting's impact on workers' sleep depends on preference mismatch, with a higher risk of insomnia among those who prefer telecommuting but are unable to utilize it.
Cardiovascular Responses to Occupational Physical Activity Are Exaggerated by Work-Related Stress and Low Fitness
Authors: Quinn Tyler D. , Bruehwiler Timothy , Chantler Paul D. , Gibbs Bethany Barone
Published: July 2024

Objectives

Paradoxical associations between high occupational physical activity (OPA) and cardiovascular disease may be explained by exaggerated cardiovascular responses from high work-related stress or low worker fitness.

Methods

OPA, blood pressure (BP), heart rate (HR), and rate-pressure product (RPP; HR × BP) were measured objectively for 24 hours in 19 male workers. Work-related stress was measured using the Stress in General Scale. Fitness was estimated using a submaximal treadmill test. Effect modification by work-related stress and fitness on associations between OPA and cardiovascular responses was examined using mixed models with interactions.

Results

Associations between OPA and RPP, HR, and BP were stronger with high stress (P < 0.05). Associations of work-time moderate and vigorous physical activity and RPP were attenuated with higher fitness (P < 0.05).

Conclusions

OPA performed under high work-related stress or by workers with low fitness may exaggerate cardiovascular responses to OPA.
Measuring transparency in the social sciences: political science and international relations
Authors: Scoggins Bermond , Robertson Matthew P.
Published: July 2024

The scientific method is predicated on transparency—yet the pace at which transparent research practices are being adopted by the scientific community is slow. The replication crisis in psychology showed that published findings employing statistical inference are threatened by undetected errors, data manipulation and data falsification. To mitigate these problems and bolster research credibility, open data and preregistration practices have gained traction in the natural and social sciences. However, the extent of their adoption in different disciplines is unknown. We introduce computational procedures to identify the transparency of a research field using large-scale text analysis and machine learning classifiers. Using political science and international relations as an illustrative case, we examine 93 931 articles across the top 160 political science and international relations journals between 2010 and 2021. We find that approximately 21% of all statistical inference papers have open data and 5% of all experiments are preregistered. Despite this shortfall, the example of leading journals in the field shows that change is feasible and can be effected quickly.
Salmon hatchery strays can demographically boost wild populations at the cost of diversity: quantitative genetic modelling of Alaska pink salmon
Authors: May Samuel A. , Shedd Kyle R. , Gruenthal Kristen M. , Hard Jeffrey J. , Templin William D. , Waters Charles D. , Adkison Milo D. , Ward Eric J. , Habicht Christopher , Wilson Lorna I. , Wertheimer Alex C. , Westley Peter A. H.
Published: July 2024

Hatcheries are vital to many salmon fisheries, with inherent risks and rewards. While hatcheries can increase the returns of adult fish, the demographic and evolutionary consequences for natural populations interacting with hatchery fish on spawning grounds remain unclear. This study examined the impacts of stray hatchery-origin pink salmon on natural population productivity and resilience. We explored temporal assortative mating dynamics using a quantitative genetic model that assumed the only difference between hatchery- and natural-origin adults was their return timing to natural spawning grounds. This model was parameterized with empirical data from an intensive multi-generational study of hatchery–wild interactions in the world’s largest pink salmon fisheries enhancement program located in Prince William Sound, Alaska. Across scenarios of increasing hatchery fish presence on spawning grounds, our findings underscore a trade-off between demographic enhancement and preservation of natural population diversity. While enhancement bolstered natural population sizes towards local carrying capacities, hatchery introgression reduced variation in adult return timing by up to 20%. Results indicated that hatchery-origin alleles can rapidly assimilate into natural populations, despite the reduced fitness of hatchery fish attributable to phenotypic mismatches. These findings elucidate the potential for long-term demographic and evolutionary consequences arising from specific hatchery–wild interactions, emphasizing the need for management strategies that balance demographic enhancement with the conservation of natural diversity.
Injection-induced basement seismicity beneath the Raton Basin: constraints from refined fault architectures and basin structure
Authors: Wang Ruijia , Onyango Evans A. , Schmandt Brandon , Worthington Lindsay
Published: June 2024

Intraplate earthquakes induced by anthropogenic fluid injection present unexpected seismic risk to previously quiescent or low seismicity-rate regions. Despite many studies of induced seismicity, there are relatively few with detailed openly accessible constraints on the interaction between seismic sources and subsurface structures. In this study of the Raton Basin, we refine source observations from a dense nodal array and constrain basin structure using teleseismic receiver functions. The cross-correlation-based relocated hypocentres and a new set of focal mechanisms light up active fault segments and show clear spatiotemporal patterns. The geometric complexity of reactivated fault clusters appears greatest near higher rate injection wells. Simpler normal fault structure is found farther from injection wells and near abrupt structural transitions suggested by receiver functions. While less induced seismicity in the crystalline basement is expected when injection is >1 km from the top of the basement (like Raton), our receiver function analysis identified a basin thickness ~3 km beneath the nodal array and lateral variations in sedimentary structures. Our results explain potential fluid connectivity between the injection depths focused at ~1–1.5 km below the surface and basement fault activity that begins at ~3 km and reaches peak activity at ~4–8 km depths.

This article is part of the theme issue ‘Induced seismicity in coupled subsurface systems’.
Fluid-driven aseismic fault slip with permeability enhancement and dilatancy
Authors: Dunham Eric M.
Published: June 2024

Injection-induced seismicity and aseismic slip often involve the reactivation of long-dormant faults, which may have extremely low permeability prior to slip. In contrast, most previous models of fluid-driven aseismic slip have assumed linear pressure diffusion in a fault zone of constant permeability and porosity. Slip occurs within a frictional shear crack whose edge can either lag or lead pressure diffusion, depending on the dimensionless stress-injection parameter that quantifies the prestress and injection conditions. Here, we extend this foundational work by accounting for permeability enhancement and dilatancy, assumed to occur instantaneously upon the onset of slip. The fault zone ahead of the crack is assumed to be impermeable, so fluid flow and pressure diffusion are confined to the interior, slipped part of the crack. The confinement of flow increases the pressurization rate and reduction of fault strength, facilitating crack growth even for severely understressed faults. Suctions from dilatancy slow crack growth, preventing propagation beyond the hydraulic diffusion length. Our new two-dimensional and three-dimensional solutions can facilitate the interpretation of induced seismicity data sets. They are especially relevant for faults in initially low permeability formations, such as shale layers serving as caprock seals for geologic carbon storage, or for hydraulic stimulation of geothermal reservoirs.

This article is part of the theme issue ‘Induced seismicity in coupled subsurface systems’.
High efficient chromatin conformation capture without pre-enrichment (HiChew) in single cells
Authors: Chen Zhichao , Xie Yeming , Tan Chen , Ruan Fengying , Luo Meng , Zhang Chen , Guo Mei , Fang Yitong , Tang Chong
Published: June 2024

This study presents HiChew, a cutting-edge technique for high-efficiency chromatin conformation capture in single cells, without the need for pre-enrichment. This unique approach minimizes the risk of cell or DNA loss. When compared to Dip-C, HiChew captures valid pairs with 4-8 times more efficiency, reducing wastage and saving significant sequencing budget. Furthermore, HiChew delivers a lower false positive ratio, ensuring data accuracy. It also achieves more contacts per cell, enhancing resolution in single cell. HiChew’s superior performance not only enhances single-cell Hi-C but also streamlines conventional Hi-C, making it more robust than conventional HiC methods. This study also unveils a fascinating mechanism of gene activation in the B compartment of chromatin, providing insight into the elusive aspect of gene expression within this region.
Striking Long Term Beneficial Effects of Single Dose Psilocybin and Psychedelic Mushroom Extract in the SAPAP3 Rodent Model of OCD-Like Excessive Self-Grooming
Authors: Brownstien Michal , Lazar Michal , Botvinnik Alexander , Shevakh Chloe , Blakolmer Karin , Lerer Leonard , Lifschytz Tzuri , Lerer Bernard
Published: June 2024

Obsessive compulsive disorder (OCD) is a highly prevalent disorder that causes serious disability. Available treatments leave 40% or more of people with OCD significantly symptomatic. There is an urgent need for novel therapeutic approaches. Mice that carry a homozygous deletion of the SAPAP3 gene (SAPAP3 KO) manifest a phenotype of excessive self-grooming, tic-like head-body twitches and anxiety. These behaviors closely resemble pathological self-grooming behaviors observed in humans in conditions that overlap with OCD. Following a preliminary report that the tryptaminergic psychedelic, psilocybin, may reduce symptoms in patients with OCD, we undertook a randomized controlled trial of psilocybin in 50 SAPAP3 KO mice (28 male, 22 female). Mice that fulfilled inclusion criteria were randomly assigned to a single intraperitoneal injection of psilocybin (4.4 mg/kg), psychedelic mushroom extract (encompassing the same psilocybin dose) or vehicle control and were evaluated after 2, 4 and 21 days by a rater blind to treatment allocation for grooming characteristics, head-body twitches, anxiety and other behavioral features. Mice treated with vehicle (n=18) manifested a 118.71+95.96 % increase in total self-grooming (the primary outcome measure) over the 21-day observation period. In contrast, total self-grooming decreased by 14.60%+17.90% in mice treated with psilocybin (n=16) and by 19.20+20.05% in mice treated with psychedelic mushroom extract (n=16) (p=.001 for effect of time; p=.0001 for time X treatment interaction). 5 mice were dropped from the vehicle group because they developed skin lesions; 4 from the psilocybin group and none from the psychedelic mushroom extract group. Secondary outcome measures such as head-body twitches and anxiety all showed a significant improvement over 21 days. Notably, in mice that responded to psilocybin (n=12) and psychedelic mushroom extract (n=13), the beneficial effect of a single treatment persisted up to 7 weeks. Mice initially treated with vehicle and non-responsive, showed a clear and lasting therapeutic response when treated with a single dose of psilocybin or psychedelic mushroom extract and followed for a further 3 weeks. While equivalent to psilocybin in overall effect on self-grooming, psychedelic mushroom extract showed superior effects in alleviating head-body twitches and anxiety. These findings strongly justify clinical trials of psilocybin in the treatment of OCD and further studies aimed at elucidating mechanisms that underlie the long-term effects to alleviate excessive self-grooming observed in this study.

Graphical Abstract

Prepared with BioRender (https://www.biorender.com/)
First Draft Genome of the Corn LeafhopperDalbulus maidis: A Transparent, Open, and Updateable Resource in the Context of Agricultural Emergence
Authors: Debat Humberto Julio , Fernández Franco
Published: June 2024

The corn leafhopper,Dalbulus maidis, is a significant pest affecting maize crops, causing extensive economic losses and posing a threat to food security. This study presents the first draft genome ofD. maidisas part of a comprehensive initiative to generate critical information for effective pest management and long-term control strategies. The genome sequencing is being conducted using a hybrid approach that integrates Oxford Nanopore Technologies (ONT) and Illumina platforms, ensuring high accuracy and depth. The initial genome assembly comprises approximately 580 Mb, with an N50 of 50,453 bp, indicating a draft assembly quality. The genome’s completeness, evaluated using BUSCO, stands at 68.6%, underscoring the thoroughness of the assembly. This first draft genome is designed to be a “living genome,” subject to continuous updates as new sequencing data become available. By providing an open and updatable genomic resource, this study aims to facilitate ongoing research and foster collaborative efforts in developing innovative solutions to mitigate the impact ofD. maidison maize cultivation.
Single-nucleus multiomics reveals the disrupted regulatory programs in three brain regions of sporadic early-onset Alzheimer’s disease
Authors: Liu Andi , Citu Citu , Enduru Nitesh , Chen Xian , Manuel Astrid M. , Sinha Tirthankar , Gorski Damian , Fernandes Brisa S. , Yu Meifang , Schulz Paul E. , Simon Lukas M. , Soto Claudio , Zhao Zhongming
Published: June 2024

Sporadic early-onset Alzheimer’s disease (sEOAD) represents a significant but less-studied subtype of Alzheimer’s disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type-specific transcriptomic changes and linked candidatecis-regulatory elements (cCREs) across brain regions. We prioritized seven conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells and neurons, highlighting their regulatory potential on gene expression in receiver cells. We reported 38 cCREs linked to sEOAD-associated genes overlapped with late-onset AD risk loci, and sEOAD cCREs enriched in neuropsychiatric disorder risk loci. This atlas helps dissect transcriptional and chromatin dynamics in sEOAD, providing a key resource for AD research.
Post-transcriptional regulation by the CCR4-NOT deadenylase complex maintains redox homeostasis in insulin biosynthesis in mouse pancreatic β cells
Authors: Yanagiya Akiko , Stoney Patrick N. , Tara Yuki , Takaoka Shohei , Vares Guillaume , Higa Rei , Friedman Nicholas R. , Villar-Briones Alejandro , Yamamoto Tadashi
Published: June 2024

Pancreatic β cells synthesize insulin to maintain glucose homeostasis. In diabetes, elevated blood glucose and insulin resistance compel β cells to produce insulin, and hence β cells are vulnerable to oxidative stress by glucotoxicity. In insulin biosynthesis, the conversion of proinsulin to insulin is initiated by forming disulfide bonds in proinsulin for oxidative protein folding. Insulin content and insulin secretion in β cells are decreased by deletion of CNOT7, a catalytic subunit of the CCR4-NOT complex, and accompanied by increased proinsulin, implying the impaired conversion of proinsulin to insulin. We found that PRDX4 essential for disulfide bond formation in proinsulin, is reduced inCnot7-KO β cells. Moreover, protein expression of CNOT8, a paralog of CNOT7, is increased inCnot7-KO β cells and binds toPrdx4mRNA via MSI2. Here, we demonstrate the post-transcriptional regulation ofPrdx4mRNA by the CCR4-NOT complex to maintain oxidative-reductive homeostasis in insulin biosynthesis.

HIGHLIGHTS

Insulin content and secretion are decreased inCnot7-KO pancreatic β cells.

PRDX4, needed for proinsulin folding, is decreased inCnot7-KO pancreatic islets.

The conversion of proinsulin to insulin is impaired inCnot7-KO β cells.

CNOT8, but not CNOT7, interacts with MSI2 that binds toPrdx4mRNA
Synthetic augmentation of cancer cell line multi-omic datasets using unsupervised deep learning
Authors: Cai Zhaoxiang , Apolinário Sofia , Baião Ana R. , Pacini Clare , Sousa Miguel D. , Vinga Susana , Reddel Roger R , Robinson Phillip J. , Garnett Mathew J. , Zhong Qing , Gonçalves Emanuel
Published: June 2024

Multi-omic characterization and integration remains a challenge due to data complexity and sparsity. Addressing this, our study introduces an unsupervised deep learning model, MOVE (Multi-Omic Variational Encoder), specifically designed to integrate and augment the Cancer Dependency Map (DepMap). Harnessing orthogonal multi-omic information, this model successfully generates molecular and phenotypic profiles, resulting in an increase of 32.7% in the number of multi-omic profiles and thereby generating a complete DepMap for 1,523 cancer cell lines. The synthetically enhanced data increases statistical power, uncovering less studied mechanisms associated with drug resistance, and refines the identification of genetic associations and clustering of cancer cell lines. By applying SHAP for model interpretation, MOVE reveals multi-omic features essential for cell clustering and biomarker identification related to drug and gene dependencies. This understanding is crucial for the development of much-needed, effective strategies in prioritizing cancer targets.