bluuebunny/crossref_metadata_2025 huggingface dataset:
EVALUATION OF QUALITY OF LIFE AND RECURRENCE RATE AFTER LAPAROSCOPIC VENTRAL HERNIA REPAIR: A COMPARATIVE STUDY OF IPOM VS IPOM PLUS
Authors: Pepe F , Giaccone M , Gambali E , Rosati S , Sandrucci S
Published: May 2024

Background

Intraperitoneal Onlay Mesh (IPOM) and IPOM plus are well-established techniques for the repair ventral hernias. IPOM plus could reduce recurrence but evidence regarding the post-operative Quality of Life (QoL) is still missing. This retrospective observational study aims to evaluate the difference in terms of recurrence rate, complication rate and postoperative QoL outcomes in patients who underwent IPOM or IPOM plus repair.

Materials and Methods

110 patients who underwent laparoscopic ventral hernia repair from 2011 to 2023 have been included in this analysis. All procedures were conducted following the standard IPOM procedure using polypropylene composite meshes (1) fixated with resorbable takers. In cases where IPOM Plus was performed, the defect was closed using transparietal sutures. Baseline characteristics and data for all patients were gathered from hospital medical records. QoL was evaluated using the EuraHS-QoL questionnaire. The primary endpoints of the study were the recurrence rate and the post-operative QoL in two subgroups: IPOM (na = 37) and IPOM Plus (nb = 80)

Results

The two groups didn’t show significant differences in baseline and hernia characteristics. With a comparable follow-up time, recurrence was significantly higher in the IPOM group (na = 10,8% vs. nb = 0% p <0.001) without any difference regarding the complications rate. Both techniques show comparable improvements in the post-operative QoL.

Conclusion

Our clinical experience showed that both IPOM or IPOM plus techniques utilizing polypropylene composite meshes are safe and effective approaches for the treatment of primary and incisional hernias. We recommend prioritizing IPOM Plus over IPOM alone due to the lower recurrence rate and comparable QoL outcomes.

(ClearMesh-Composite, Dipromed srl)
IS THERE A PLACE FOR INTRAPERITONEAL ONLAY MESH(IPOM) FOR INGUINAL HERNIA? A SINGLE-CENTRE EXPERIENCE
Authors: Pepe F , Gambali E , Giaccone M
Published: May 2024

Background

IPOM is a well-established technique for the laparoscopic treatment of ventral hernias, for which it can also be considered the treatment of choice in selected patients. Its usage for the laparoscopic treatment of inguinal hernia has already been described. The main concern about this technique is the high risk of neurovascular damage since mesh fixation has always been achieved with resorbable tackers. Recently, some new glue-based fixation devices have been introduced that could almost nullify this risk. This study aims to evaluate the feasibility of IPOM techniques for inguinal hernia treatment using only glue-based fixation devices.

Materials and Methods

Sixteen patients (13 with bilateral inguinal hernias) who underwent IPOM inguinal hernia repair from 2021 to 2023 were included. All patient data were collected from the hospital's medical records. Follow-up appointments were scheduled for clinical visits every 3 months during the first year, and every 6 months thereafter to evaluate long-term outcomes.

Results

The mean follow-up time was 13.2 ± 6.8 months. The mean operative time was 22.5 ± 6.8 minutes and all the patients were discharged a one-night stay. Only one case of unilateral recurrence was reported. Complications occurred in 2 patients (Grade I according to the Clavien-Dindo scale). No cases of intraoperative bleeding or chronic pain were reported.

Conclusion

Our experience shows that the IPOM technique with glue-based fixation devices is a safe, feasible and easy-to-master method for the treatment of inguinal hernias. Due to its main characteristic such as the short execution time, it could be considered as an option for selected patients, particularly in cases of synchronous interventions. Further trials are needed to evaluate the clinical outcomes.
RECURRENCE RATE AND QUALITY OF LIFE IN OPEN INGUINAL HERNIA REPAIR: A COMPARATIVE STUDY OF LICHTENSTEIN VS TRABUCCO REPAIR
Authors: Pepe F , Giaccone M , Gambali E , Palazzo V , Rosati S , Sandrucci S
Published: May 2024

Background

The aim of this retrospective observational study with prospective follow-up is to evaluate the clinical outcomes and patients' Quality of Life (QoL) after either a Lichtenstein or a Trabucco inguinal hernia repair.

Materials and Methods

532 patients who underwent inguinal hernia repair from 2016 to 2022 were included in this analysis. All the patients' baseline characteristics and data were collected from the hospital medical records. A phone interview was conducted to investigate long-term outcomes and patients’ QoL (EuraHS-QoL questionnaire) was performed between December 2022 and January 2024. The primary endpoint was the evaluation of patients’ recurrence rate and QoL in two technique groups: Lichtenstein (nA = 391) or Trabucco (nB = 141).

Results

The two groups didn’t show significant differences in main baseline characteristics. With a comparable median follow-up, no differences in complication rate (nA = 10.2% vs. nb= 11.3% p = 0.78) and recurrence rate (nA = 7.9% vs. nb = 4.96% p = 0.08)were detected among the two groups. Patients’ QoL improvement compared to the baseline was statistically significant in both groups. On the other hand, the weight of the mesh appears to have no impact on clinical outcomes (such as recurrence and complications), but it could worsen QoL when a heavier mesh is employed.

Conclusion

This analysis did not reveal any significant differences in outcomes between the two primary inguinal hernia repair techniques. Based on our experience, the choice of surgical techniques could be made depending on the preferences of the surgeons. It is crucial to select the weight of the mesh carefully.
THE INCIDENCE OF ADDITIONAL HERNIA DEFECTS IN A DIASTATIC LINEA ALBA, NOT REPORTED ON PRE-OPERATIVE CT IMAGING
Authors: Sharma A , Simpson G
Published: May 2024

Aim

Patients with ventral primary or incisional hernias with significant recti diastasis are frequently refered to abdominal wall reconstruction (AWR) services. We audited the rate of incidental intra-operative ventral defects related to diastatic linea alba.

Method

A retrospective analysis of a prospectively maintained database was carried out from March 2023 to January 2024. All patients who underwent AWR using a minimally invasive approach (MIS) were included. Data on the following variables were collected: sex, age (years), BMI (kg/m2), length of hospital stay (LOS, days), operative time (hours), and ventral defects.

Results

27 patients underwent MIS AWR (22 robotic; 8 laparoscopic). Male to female ratio was 16:11. Median age was 58 years (IQR 48–66) and BMI 36 kg/m2 (IQR 32–37). All patients underwent eTEP retro-rectus Rives-Stoppa + diastasis plication using macroporous polypropylene non-absorbable synthetic mesh. Median operating time was 3.3 hours (IQR 3.1–3.5) and LOS was 2 days (IQR 1–2). 1 (3%) patient had laparoscopic converted to open procedure due to bowel involvement.

13 (48%) of patients had extra defects associated with diastatic linea alba which were not visualized in pre-operative cross-sectional imagining.

Conclusion

When compared to a local repair, the MIS AWR approach in patients with ventral hernias and significant diastasis is justified when considering the high likelihood of synchronous linea alba defects and therefore a risk for future recurrence. These extra defects are rarely detected on pre-operative cross-sectional images. In addition, the plication of diastasis during AWR allows surgeons to recreate a more functional linea alba.
PREDICTION OF SUCCESSFUL REVISION SURGERY FOR MESH-RELATED COMPLAINTS AFTER INGUINAL HERNIA AND PELVIC ORGAN PROLAPSE REPAIR
Authors: van Rest K L C , Gielen M J C A M , Warmerdam L M , Kowalik C R , Roovers J P W R , Zwaans W A R
Published: May 2024

Purpose

With this retrospective case series, we aim to identify predictors for reduction of pain after mesh revision surgery in patients operated for inguinal hernia or pelvic organ prolapse with a polypropylene implant. Identifying these predictors may aid surgeons to counsel patients and select appropriate candidates for mesh revision surgery.

Methods

Clinical records before and after mesh revision surgery from 221 patients with chronic postoperative inguinal pain (CPIP) and 59 patients with pain after pelvic organ prolapse (POP) surgery were collected at two experienced tertiary referral centers. Primary outcome was patient reported improvement of pain after revision surgery. A multivariable logistic regression model was used to specify predictors for pain reduction.

Results

The multivariable logistic regression was performed for each patient group separately. Patients with CPIP had higher chances of improvement of pain when time between mesh placement and mesh revision surgery was longer, with an OR of 1.19 per year. A turning point in chances of risks and benefits was demonstrated at 70 months, with improved outcomes for patients with revision surgery ≥70 months (OR 2.86). For POP patients, no statistically significant predictors for reduction of pain after (partial) removal surgery could be identified.

Conclusion

A longer duration of at least 70 months between implantation of inguinal mesh and revision surgery seems to give a higher chance on improvement of pain. Caregivers should not avoid surgery based on a longer duration of symptoms when an association between symptoms and the location of the mesh is found.
THE VERY FIRST EXPERIENCE WITH eTEP IN OUR DEPARTMENT
Authors: Woleský J , Jíšová B , East B
Published: May 2024

Background

Nowadays the main method everybody is talking about in ventral hernia repair is eTEP. The retromuscular hernia repair seems to be the gold standard for ventral hernias. The occurrence of ventral hernias is around 20% for primary and 30% for incisional hernias following the midline incisions. There is a surge of surgeons who are diving into this relatively new mini-invasive method. Until 2022 we performed only open ventral hernia repairs. Therefore, we have decided that we cannot be stuck "in the past" and started our long way of learning and improving in the eTEP field.

Method

We have run a retrospective trial looking at our small cohort of patients with ventral hernias that have undergone eTEP procedure at our department in the University hospital. We have specifically focused on the conversion rate to open surgery, possible complications, operating times, and postoperative complications.

Results

14 patients have successfully undergone the eTEP hernia repair. We had to convert 5 of those cases. The main surgical accident resulting in conversion was the perforation of peritoneum and entering the abdominal cavity. There were no sever complications and the most common postoperative complication was hematoma with no need of surgical revision.

Conclusion

Our first experience with the eTEP has been challenging and as the results show that we need to improve in many surgical categories. Especially in developing the retromuscular space. Also, lately we have managed to schedule easier cases with primary hernias and the results became better immediately.
OPEN REPAIR OF A LARGE VENTRAL HERNIA REQUIRING CAECOPEXY AND APPENDICECTOMY IN AN ELDERLY PATIENT
Authors: Zhao S , Abdulla M , Gerogiannis I
Published: May 2024

Aim

To present an interesting and challenging case of a large ventral hernia repair requiring caecopexy and appendectomy.

Material and Methods

An 83-year-old woman with hypothyroidism and hypertension but no other comorbidities presented to the outpatient clinic with a very large hernia which she said had been present for 20 years. On clinical examination the hernia was very large and irreducible containing bowel. The CT scan of the abdomen and pelvis showed a defect of 5 cm with a sac of 21 cm width containing loops of both large and small bowel including the entire right and transverse colon.

The procedure comprised skin incision followed by dissection of the sac from the skin and subcutaneous fat. The neck of the hernial sac was identified and opened. Safe entry into the abdomen. Minor adhesiolysis of the omentum from the sac. Small bowel was traced from the ileocaecal junction to the duodenojejunal flexure. Appendix identified and removed. Caecum and ascending colon were reduced in the peritoneal cavity and fixed to the lateral abdominal wall with non-absorbable sutures (caecopexy). Small and large bowel were placed in anatomical position. A small part of the omentum was removed. Rives-Stoppa technique was used. The right and left rectus sheaths were opened the posterior rectus sheath was identified and the retrorectus space was developed. Neurovascular bundles were identified and preserved. Dissection continued towards the xiphisternum and pubis.

The posterior rectus sheaths (right and left) were sutured together. A 30 × 30 lightweight microporous mesh was deployed into the retrorectus space. The anterior rectus sheath was closed with a non-absorbable suture. Haemostasis was achieved. 2 negative pressure 14 French drains were placed over the mesh in the retrorectus space. Another drain was placed in the subcutaneous space.

Results

The patient's post-operative course was uneventful, she remained in intensive care for 5 days and was discharged after 2 weeks of ward care. Her discharge was delayed due to the need for extensive physiotherapy. At 6 months follow-up, the patient was well and satisfied with the outcome of the procedure.

Conclusion

Ventral hernia repair in elderly patients can be challenging and have a long recovery, in some cases a combined intrabdominal approach is feasible with good outcomes. A surgeon with an interest and experience in abdominal wall surgery can offer a safe and efficient approach to these cases.
Localization of stuttering based on causal brain lesions
Authors: Theys Catherine , Jaakkola Elina , Melzer Tracy R , De Nil Luc F , Guenther Frank H , Cohen Alexander L , Fox Michael D , Joutsa Juho
Published: May 2024

Stuttering affects approximately 1 in 100 adults and can result in significant communication problems and social anxiety. It most often occurs as a developmental disorder but can also be caused by focal brain damage. These latter cases may lend unique insight into the brain regions causing stuttering.

Here, we investigated the neuroanatomical substrate of stuttering using three independent datasets: (i) case reports from the published literature of acquired neurogenic stuttering following stroke (n = 20, 14 males/six females, 16–77 years); (ii) a clinical single study cohort with acquired neurogenic stuttering following stroke (n = 20, 13 males/seven females, 45–87 years); and (iii) adults with persistent developmental stuttering (n = 20, 14 males/six females, 18–43 years). We used the first two datasets and lesion network mapping to test whether lesions causing acquired stuttering map to a common brain network. We then used the third dataset to test whether this lesion-based network was relevant to developmental stuttering.

In our literature dataset, we found that lesions causing stuttering occurred in multiple heterogeneous brain regions, but these lesion locations were all functionally connected to a common network centred around the left putamen, including the claustrum, amygdalostriatal transition area and other adjacent areas. This finding was shown to be specific for stuttering (PFWE < 0.05) and reproducible in our independent clinical cohort of patients with stroke-induced stuttering (PFWE < 0.05), resulting in a common acquired stuttering network across both stroke datasets. Within the common acquired stuttering network, we found a significant association between grey matter volume and stuttering impact for adults with persistent developmental stuttering in the left posteroventral putamen, extending into the adjacent claustrum and amygdalostriatal transition area (PFWE < 0.05).

We conclude that lesions causing acquired neurogenic stuttering map to a common brain network, centred to the left putamen, claustrum and amygdalostriatal transition area. The association of this lesion-based network with symptom severity in developmental stuttering suggests a shared neuroanatomy across aetiologies.
Punishment, communities and assemblages
Authors: Ruggiero Vincenzo
Published: May 2024

Punishment is not only meted out in custodial institutions. It is also inflicted on ‘free’ individuals who experience harsh material conditions, violent institutional control or punitive responses to their political views and actions. This paper addresses punishment beyond the prison walls, where a variety of counter-hegemonic identities are moulded and where radical approaches to punishment are gestated. The argument is made that the abolitionist movement may find among those identities a range of potential allies for its campaigns. Key allies may also be found among community development activists and programmes.
Sustainability assessment of solar drying systems: a comparative life-cycle analysis of phase-change material-based vs. cylindrical solar dryers
Authors: Divyangkumar Nakum , Sharma Kirtika , Panwar N L , Saichandhu Gande
Published: May 2024

Solar drying systems are becoming a popular alternative to traditional energy-based drying systems for agricultural products due to their effectiveness and reduced fuel consumption. Although the efficiency of solar drying systems has been thoroughly investigated, their sustainability has not been studied enough. This study aims to fill that gap by conducting a life-cycle assessment of two new solar drying systems built in Udaipur, Rajasthan, India. The environmental implications of an innovative cylindrical solar-assisted drying system and a phase-change material-based solar drying system were evaluated using cradle-to-gate life-cycle analysis. The study uses the ReCiPe 2016 endpoints (H) technique to calculate various aspects such as midpoint, endpoint, single score, normalization result, and network diagram for phase-change material-based solar drying and cylindrical solar-assisted drying. Results show that phase-change material-based solar drying has an average of 40% more impact on the environment than cylindrical solar-assisted drying, with a high impact found in human non-carcinogenic toxicity, mainly due to the production of phase-change materials. However, cylindrical solar-assisted drying system crossover phase-change material based solar drying in terms of its impact on human carcinogenic toxicity and fossil resource scarcity. The contribution to global warming of phase-change material-based solar drying is 13.7% more than that of cylindrical solar-assisted drying. The endpoint characterization indicates that phase-change material-based solar drying exceeds in terms of human health (40%) and ecosystem (37.04%), whereas cylindrical solar-assisted drying surpasses phase-change material-based solar drying in terms of impacts on resources, at 14%. The early drying in phase-change material-based solar drying makes up for its higher impact than that in cylindrical solar-assisted drying, which takes 3 hours longer to dry. This study offers guidance and methods for making the best choice of solar-powered dryers.
SARS-CoV-2 Vaccination in the First Year After Hematopoietic Cell Transplant or Chimeric Antigen Receptor T-Cell Therapy: A Prospective, Multicenter, Observational Study
Authors: Hill Joshua A , Martens Michael J , Young Jo-Anne H , Bhavsar Kavita , Kou Jianqun , Chen Min , Lee Lik Wee , Baluch Aliyah , Dhodapkar Madhav V , Nakamura Ryotaro , Peyton Kristin , Howard Dianna S , Ibrahim Uroosa , Shahid Zainab , Armistead Paul , Westervelt Peter , McCarty John , McGuirk Joseph , Hamadani Mehdi , DeWolf Susan , Hosszu Kinga , Sharon Elad , Spahn Ashley , Toor Amir A , Waldvogel Stephanie , Greenberger Lee M , Auletta Jeffery J , Horowitz Mary M , Riches Marcie L , Perales Miguel-Angel
Published: May 2024

Background

The optimal timing of vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines after cellular therapy is incompletely understood. The objectives of this study are to determine whether humoral and cellular responses after SARS-CoV-2 vaccination differ if initiated <4 months versus 4–12 months after cellular therapy.

Methods

We conducted a multicenter, prospective, observational study at 30 cancer centers in the United States. SARS-CoV-2 vaccination was administered as part of routine care. We obtained blood prior to and after vaccinations at up to 5 time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2–specific T-cell receptors, in a subgroup.

Results

We enrolled 466 allogeneic hematopoietic cell transplantation (HCT) (n = 231), autologous HCT (n = 170), and chimeric antigen receptor T-cell (CAR-T-cell) therapy (n = 65) recipients between April 2021 and June 2022. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months versus 4–12 months after cellular therapy. Anti-S IgG ≥2500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T-cell recipients, respectively. SARS-CoV-2–specific T-cell responses were attained in 57%, 83%, and 58%, respectively. Pre–cellular therapy SARS-CoV-2 infection or vaccination and baseline B-cell count were key predictors of post–cellular therapy immunity.

Conclusions

These data support mRNA SARS-CoV-2 vaccination prior to, and reinitiation 3 to 4 months after, cellular therapies with allogeneic HCT, autologous HCT, and CAR-T-cell therapy.
Exploring the sex difference in cardiovascular risk during growth hormone therapy in adults
Authors: Slagboom Tessa N A , van der Lely Aart Jan , Drent Madeleine L , van Bunderen Christa C
Published: May 2024

Objective

Given the previously identified sex differences in cardiovascular (CV) morbidity and mortality in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT), our aim is to investigate sex-specific differences in the efficacy of (long-term) GHRT on CV risk profile and disease in subjects with GHD. Our hypothesis is that women will experience less beneficial effects than men.

Design

Retrospective nationwide cohort study.

Methods

We compared all men (n = 1335) and women (n = 1251) with severe GHD registered in the Dutch National Registry of GH Treatment in Adults database with respect to CV risk profile and morbidity at baseline and during follow-up.

Results

Men had a more unfavourable CV risk profile at baseline. During the first years of GHRT, the reduction in waist circumference, waist-to-hip ratio, total cholesterol, and triglyceride levels was greater in men than in women (all P < .05). Between-sex differences in effects during later follow-up were less clear. No sex differences were found in the risk of developing non-fatal cardiovascular or cerebrovascular diseases during GHRT.

Conclusions

Our results suggest that men with GHD did indeed experience more beneficial effects of GHRT on body composition and lipoprotein metabolism than women, at least in the early years of treatment. Also, the more unfavourable CV risk profile at baseline in men did not translate into a sex difference in the risk of developing CV and cerebrovascular morbidity during GHRT.
Telephone triage of chest pain in out-of-hours primary care: external validation of a symptom-based prediction rule to rule out acute coronary syndromes
Authors: Manten Amy , Harskamp Ralf E , Busschers Wim B , Moll van Charante Eric P , Himmelreich Jelle C L
Published: May 2024

Introduction

Telephone triage is pivotal for evaluating the urgency of patient care, and in the Netherlands, the Netherlands Triage Standard (NTS) demonstrates moderate discrimination for chest pain. To address this, the Safety First Prediction Rule (SFPR) was developed to improve the safety of ruling out acute coronary syndrome (ACS) during telephone triage.

Methods

We conducted an external validation of the SFPR using data from the TRACE study, a retrospective cohort study in out-of-hours primary care. We evaluated the diagnostic accuracy assessment for ACS, major adverse cardiovascular events (MACE), and major events within 6 weeks. Moreover, we compared its performance with that of the NTS algorithm.

Results

Among 1404 included patients (57.3% female, 6.8% ACS, 8.6% MACE), the SFPR demonstrated good discrimination for ACS (C-statistic: 0.79; 95%-CI: 0.75–0.83) and MACE (C-statistic: 0.79; 95%-CI: 0.0.76–0.82). Calibration was satisfactory, with overestimation observed in high-risk patients for ACS. The SFPR (risk threshold 2.5%) trended toward higher sensitivity (95.8% vs. 86.3%) and negative predictive value (99.3% vs. 97.6%) with a lower negative likelihood ratio (0.10 vs. 0.34) than the NTS algorithm.

Conclusion

The SFPR proved robust for risk stratification in patients with acute chest pain seeking out-of-hours primary care in the Netherlands. Further prospective validation and implementation are warranted to refine and establish the rule’s clinical utility.
Insights into ribosomal DNA dominance and magnification through characterization of isogenic deletion alleles
Authors: Kindelay Selina M , Maggert Keith A
Published: May 2024

The major loci for the large primary ribosomal RNA (rRNA) genes (35S rRNAs) exist as hundreds to thousands of tandem repeats in all organisms and dozens to hundreds in Drosophila. The highly repetitive nature of the ribosomal DNA (rDNA) makes it intrinsically unstable, and many conditions arise from the reduction in or magnification of copy number, but the conditions under which it does so remain unknown. By targeted DNA damage to the rDNA of the Y chromosome, we created and investigated a series of rDNA alleles. We found that complete loss of rDNA leads to lethality after the completion of embryogenesis, blocking larval molting and metamorphosis. We find that the resident retrotransposons—R1 and R2—are regulated by active rDNA such that reduction in copy number derepresses these elements. Their expression is highest during the early first instar, when loss of rDNA is lethal. Regulation of R1 and R2 may be related to their structural arrangement within the rDNA, as we find they are clustered in the flanks of the nucleolus organizing region (NOR; the cytological appearance of the rDNA). We assessed the complex nucleolar dominance relationship between X- and Y-linked rDNA using a histone H3.3–GFP reporter construct and incorporation at the NOR and found that dominance is controlled by rDNA copy number as at high multiplicity the Y-linked array is dominant, but at low multiplicity the X-linked array becomes derepressed. Finally, we found that multiple conditions that disrupt nucleolar dominance lead to increased rDNA magnification, suggesting that the phenomena of dominance and magnification are related, and a single mechanism may underlie and unify these two longstanding observations in Drosophila.
FLN-2 functions in parallel to linker of nucleoskeleton and cytoskeleton complexes and CDC-42/actin pathways during P-cell nuclear migration through constricted spaces in Caenorhabditis elegans
Authors: Ma Linda , Kuhn Jonathan , Chang Yu-Tai , Elnatan Daniel , Luxton G W Gant , Starr Daniel A
Published: May 2024

Nuclear migration through narrow constrictions is important for development, metastasis, and proinflammatory responses. Studies performed in tissue culture cells have implicated linker of nucleoskeleton and cytoskeleton (LINC) complexes, microtubule motors, the actin cytoskeleton, and nuclear envelope repair machinery as important mediators of nuclear movements through constricted spaces. However, little is understood about how these mechanisms operate to move nuclei in vivo. In Caenorhabditis elegans larvae, six pairs of hypodermal P cells migrate from lateral to ventral positions through a constricted space between the body wall muscles and the cuticle. P-cell nuclear migration is mediated in part by LINC complexes using a microtubule-based pathway and by an independent CDC-42/actin-based pathway. However, when both LINC complex and actin-based pathways are knocked out, many nuclei still migrate, suggesting the existence of additional pathways. Here, we show that FLN-2 functions in a third pathway to mediate P-cell nuclear migration. The predicted N-terminal actin-binding domain in FLN-2 that is found in canonical filamins is dispensable for FLN-2 function; this and structural predictions suggest that FLN-2 does not function as a filamin. The immunoglobulin-like repeats 4–8 of FLN-2 were necessary for P-cell nuclear migration. Furthermore, in the absence of the LINC complex component unc-84, fln-2 mutants had an increase in P-cell nuclear rupture. We conclude that FLN-2 functions to maintain the integrity of the nuclear envelope in parallel with the LINC complex and CDC-42/actin-based pathways to move P-cell nuclei through constricted spaces.
Projecting Long-Term Care Costs Among Older Adults With ADL Disabilities and Cognitive Impairment in China
Authors: Jin Haiyu , Wu Chenkai
Published: May 2024

Background

Mounting evidence suggests that cognitive impairment is strongly associated with disability in activities of daily living (ADL disability) and long-term care (LTC) costs. However, studies forecasting future LTC costs often overlook these relationships. Consequently, this study aims to more accurately project future LTC costs in China over the next 20 years by considering the intertwined association between disability and cognitive impairment on future LTC costs.

Methods

Data were from 10 959 adults ≥65 years from the 2005–2018 waves of the Chinese Longitudinal Healthy Longevity Surveys. We used the Markov model to project the population of China and track the transition of older adults in the next 20 years between 4 disability–cognition states. We employed a 2-part model to estimate LTC costs (direct and indirect LTC costs) per capita.

Results

The proportion of disabled older adults with cognitive impairment was projected to increase from 1.4% in 2021 to 3.4% in 2040, while that of those without cognitive impairment was projected to decrease from 4.7% in 2021 to 4.5% in 2040. The direct and indirect LTC costs were projected to increase from 0.3% and 0.2% of gross domestic product (GDP) in 2021 to 1.4% and 0.7% in 2040 for disabled persons without cognitive impairment and from 0.1% and 0.1% of GDP in 2021 to 1.3% and 1.3% in 2040 for those with cognitive impairment, respectively.

Conclusions

Policy-makers could include the assessment of cognition in the LTC needs assessment and allocate more compensation to LTC insurance participants with cognitive impairment.
Whispers in the Wind: Face Mask Sampling for Mycobacterium tuberculosis Detection in Children With Pulmonary Tuberculosis
Authors: Meiwes Lennard , Kontsevaya Irina , Chesov Dumitru , Kulciţkaia Stela , Dreyer Viola , Hillemann Doris , Dlamini Qiniso , Williams Caroline , Barer Michael , Brinkmann Folke , Krüger Renate , Thee Stephanie , Kay Alexander , Mandalakas Anna Maria , Lange Christoph
Published: May 2024

Background

Recently, face mask sampling (FMS) confirmed detection of Mycobacterium tuberculosis DNA from exhaled breath in adults with tuberculosis. To date, no study has evaluated the use of FMS to detect pulmonary tuberculosis in children. We developed a method for FMS of M. tuberculosis-specific DNA in children and performed a clinical exploration to assess feasibility in children.

Methods

Face masks were spiked, analyzed on GeneXpert-Ultra, quantitative polymerase chain reaction, and targeted next-generation sequencing. Children with pulmonary tuberculosis were asked to wear 3 modified FFP2 masks for 30 minutes as part of an exploratory clinical study.

Results

Experiments with H37Ra M. tuberculosis strain showed a limit of 95% detection of 3.75 colony-forming units (95% confidence interval, 4.85–3.11) on GeneXpert-Ultra. Ten children with pulmonary tuberculosis participated in the clinical study. M. tuberculosis-specific DNA was detected on none of the face masks.

Conclusions

Pediatric FMS has a low limit of detection for M. tuberculosis-specific DNA in vitro. However, M. tuberculosis DNA was not detected in any of 30 masks worn by children with pulmonary tuberculosis. This suggests that FMS in this form may not be more effective for detecting M. tuberculosis in children with tuberculosis than existing methods.
To Know Me Is to Exonerate Me: Appeals to Character in Defense of the Willowbrook Hepatitis Study
Authors: Lynch John
Published: May 2024

The Willowbrook Hepatitis Study is one of the best-known examples of unethical medical research, but the research has always had defenders. One of the more intriguing defenses continually used was that critics did not know the researchers on the study and, therefore, could not assess their ethics. This essay traces the appeal to the researchers’ characters across published research and archival sources from the 1960s through today. These appeals reflect the observation as old as Aristotle that one of the most potent modes of persuasion is ethos or character. The specific types of character in these appeals develop out of the paternalistic nature of clinical and research practice in the mid-twentieth century. If the individual physician is the locus of medical judgment, then the physician’s character becomes a key concern for bioethics. These appeals still appear and have implications for bioethics in the present day.
Applications of artificial intelligence for machine- and patient-specific quality assurance in radiation therapy: current status and future directions
Authors: Ono Tomohiro , Iramina Hiraku , Hirashima Hideaki , Adachi Takanori , Nakamura Mitsuhiro , Mizowaki Takashi
Published: May 2024

Machine- and patient-specific quality assurance (QA) is essential to ensure the safety and accuracy of radiotherapy. QA methods have become complex, especially in high-precision radiotherapy such as intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), and various recommendations have been reported by AAPM Task Groups. With the widespread use of IMRT and VMAT, there is an emerging demand for increased operational efficiency. Artificial intelligence (AI) technology is quickly growing in various fields owing to advancements in computers and technology. In the radiotherapy treatment process, AI has led to the development of various techniques for automated segmentation and planning, thereby significantly enhancing treatment efficiency. Many new applications using AI have been reported for machine- and patient-specific QA, such as predicting machine beam data or gamma passing rates for IMRT or VMAT plans. Additionally, these applied technologies are being developed for multicenter studies. In the current review article, AI application techniques in machine- and patient-specific QA have been organized and future directions are discussed. This review presents the learning process and the latest knowledge on machine- and patient-specific QA. Moreover, it contributes to the understanding of the current status and discusses the future directions of machine- and patient-specific QA.
Estimating the proportion of modern contraceptives supplied by the public and private sectors using a Bayesian hierarchical penalized spline model
Authors: Comiskey Hannah , Alkema Leontine , Cahill Niamh
Published: May 2024

Quantifying the public/private-sector supply of contraceptive methods within countries is vital for effective and sustainable family-planning delivery. However, many low- and middle-income countries quantify contraceptive supply using out-of-date Demographic Health Surveys. As an alternative, we propose using a Bayesian, hierarchical, penalized-spline model, with survey input, to produce annual estimates and projections of contraceptive supply-share outcomes. Our approach shares information across countries, accounts for survey observational errors and produces probabilistic projections informed by past changes in supply shares, as well as correlations between supply-share changes across different contraceptive methods. Results may be used to evaluate family-planning program effectiveness and stability.
Inflammatory myofibroblastic tumor of the cecum presenting as acute abdomen, a rare pathology with a rarer presentation
Authors: Molina Gabriel A , Ludeña Carolina , Carrera Paul Alexander , Heredia Andrea E , Jimenez Galo E , Parrales Diana E , Portilla Carolina Alexandra , Martinez Sebastian Nicolay , Ochoa-Andrade Miguel Jacob
Published: May 2024

Inflammatory myofibroblastic tumor is an extremely rare neoplastic lesion with a predilection for aggressive local and recurrent behavior. The tumor tends to occur in the lungs of children and young adults, and although it can develop in older patients and other organs, this is extremely rare. Symptoms are nonspecific and depend on the location and size of the tumor. The gastrointestinal tract is rarely this mass’s primary site of origin, and the cecum is an even rarer location. We present the case of an otherwise healthy 55-year-old female who presented with an acute abdomen and a mass in her abdomen; after successful surgery, she fully recovered. Inflammatory myofibroblastic tumor causing acute abdomen was the final diagnosis.
Comparison of quantitative and qualitative anti-dsDNA assays
Authors: Selvaratnam Rajeevan , Srivastava Pooja , Tacker Danyel H , Thebo Jennifer , Wheeler Sarah E
Published: May 2024

Objective

In evaluation of systemic lupus erythematosus (SLE), anti–double-stranded DNA antibodies (anti-dsDNA) play a significant role in diagnosis, monitoring SLE activity, and assessing prognosis. However, evaluations of the performance and limitations for recently developed methods for anti-dsDNA assessment are sparse.

Methods

Specimens used for antinuclear antibody testing (n = 129) were evaluated for anti-dsDNA assay comparability across 4 medical centers in the United States. The methods compared were Werfen Quanta Lite dsDNA, Zeus Scientific dsDNA Enzyme Immunoassay, Bio-Rad multiplex immunoassay (MIA) dsDNA, ImmunoConcepts Crithidia, and Bio-Rad Laboratories Crithidia.

Results

For quantitative anti-dsDNA measurements, Spearman’s correlation coefficient was highest between Zeus and Werfen (ρ = 0.86; CI, 0.81-0.90; P < .0001). Comparison of MIA to Werfen or Zeus yielded similar results to each other (ρ = 0.58; CI, 0.44-0.68; P < .0001; and ρ = 0.59; CI, 0.46-0.69; P < .0001, respectively), but lower than the correlation between Zeus and Werfen. Positive concordance between assays ranged from 31.4% to 97.1%, and negative concordance between assays ranged from 58.5% to 100%. The detection of anti-dsDNA in those with SLE diagnosis ranged from 50.9% to 77.4% for quantitative assays and 15.1% to 24.5% for Crithidia assays.

Conclusion

Current quantitative anti-dsDNA assays are not interchangeable for patient follow-up. Crithidia-based assays demonstrate high negative concordance and lack positive concordance among the methods.
Optimizing Advanced Trauma Life Support (ATLS®) to Maximize Readiness
Authors: Danford Joseph R , Reyes Florencio , Gurney Jennifer M , Smith Joshua P , Stinner Daniel J
Published: May 2024

Introduction

The Army utilizes Individual Critical Task Lists (ICTLs) to track and ensure competency and deployment readiness of its medical service members. ICTLs are the various skills and procedures that the Army has deemed foundational for each area of concentration (AOC)/military occupational specialty (MOS). While many ICTLs involve the patient care that military medical providers regularly provide, some procedures are not as commonly performed. This, when coupled with lower patient volume at military treatment facilities (MTF), poses a challenge for maintaining skill competency and deployment readiness. Fort Campbell’s Blanchfield Army Community Hospital (BACH) has created a holistic and unique solution to meet many of these standardized requirements and support a ready medical force. By optimizing the Advanced Trauma Life Support (ATLS®) course curriculum to facilitate ICTL completion, BACH has increased its ICTL completion rates, ATLS® course exposure, and streamlined training requirements. The purpose of this article is to describe this best practice and suggest its applicability to other MTFs.

Materials and Methods

By cross-referencing the ATLS® course curriculum and appendices with ICTLs, BACH has augmented ATLS® course certification with the additional completion of 12 ICTLs. This new approach not only increases ICTL completion, but also increases ATLS® curriculum exposure to medical providers, such as Registered Nurses or Nurse Practitioners, who would not typically take ATLS®.

Results

Since starting this new approach in April 2021, 73 military medical personnel have completed the ATLS® course at BACH, with 24 different medical specialties represented. A total of 361 ICTLs have been completed with specific ICTL completion counts ranging from 13 to 48. Each ICTL tested was completed 100% of its annual requirement.

Conclusion

ATLS® is a mandatory joint interoperability standard for military physicians and it is also an Army ICTL for many AOCs/MOSs. Only counting completion of this course as one ICTL is a missed opportunity for the time spent by Army medical providers and limits the exposure of ATLS® to select AOCs/MOSs. This optimized and novel approach has been successful at BACH, suggesting its applicability at other MTFs that serve as ATLS® testing sites.
Candida lusitaniae Fungemia in Children: A multicenter case series of emerging pathogen
Authors: Snapiri Ori , Danziger Chen Rosenberg , Sachs Nimrod , Krause Irit , Zvi Haim Ben , Danino Dana , Kriger Or , Shachor-Meyouhas Yael , Averbuch Dina , Bilavsky Efraim
Published: May 2024

Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play.
Relationship between lymphocyte count and risk of infection in Japanese rheumatoid arthritis patients treated with tofacitinib
Authors: Tanaka Yoshiya , Takeuchi Tsutomu , Valdez Hernan , Collinge Mark , Zwillich Samuel H , Toyoizumi Shigeyuki , Kwok Kenneth , Hirose Tomohiro
Published: May 2024

Objectives

We characterised changes in absolute lymphocyte counts (ALCs) and lymphocyte subset counts (LSCs), and their relationship to incidence of serious infection events (SIEs) and herpes zoster (HZ) events in Japanese patients with moderate to severe rheumatoid arthritis enrolled in the tofacitinib clinical programme.

Methods

Data included 765 patients receiving tofacitinib in Phase 2, Phase 3, and long-term extension studies. ALCs/LSCs and incidence rates (patients with events/100 patient-years) of SIEs and HZ were analysed over 75 months.

Results

Median ALCs were generally stable over 75 months of treatment. Transient numerical increases from baseline in median LSCs were observed at Month 3; LSCs were generally lower than baseline for Months 36–75. SIE/HZ incidence rates were higher in patients with ALC <0.5 × 103 cells/mm3 versus those with ALC ≥0.5 × 103 cells/mm3 during tofacitinib treatment. Baseline LSCs were similar in patients with/without SIEs or HZ events.

Conclusions

SIE/HZ risk was highest in patients with ALC <0.5 × 103 cells/mm3, supporting this threshold as clinically relevant for defining increased SIE/HZ risk in Japanese patients with rheumatoid arthritis receiving tofacitinib. However, SIEs and HZ events did not necessarily occur simultaneously with confirmed lymphopenia, preventing conclusions on possible causal relationships being drawn.
Single-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA
Authors: Cheng Jordan C , Swarup Neeti , Morselli Marco , Huang Wei-Lun , Aziz Mohammad , Caggiano Christa , Kordi Misagh , Patel Abhijit A , Chia David , Kim Yong , Li Feng , Wei Fang , Zaitlen Noah , Krysan Kostyantyn , Dubinett Steve , Pellegrini Matteo , Wong David T W
Published: May 2024

Whole-genome bisulfite sequencing (BS-Seq) measures cytosine methylation changes at single-base resolution and can be used to profile cell-free DNA (cfDNA). In plasma, ultrashort single-stranded cfDNA (uscfDNA, ∼50 nt) has been identified together with 167 bp double-stranded mononucleosomal cell-free DNA (mncfDNA). However, the methylation profile of uscfDNA has not been described. Conventional BS-Seq workflows may not be helpful because bisulfite conversion degrades larger DNA into smaller fragments, leading to erroneous categorization as uscfDNA. We describe the ‘5mCAdpBS-Seq’ workflow in which pre-methylated 5mC (5-methylcytosine) single-stranded adapters are ligated to heat-denatured cfDNA before bisulfite conversion. This method retains only DNA fragments that are unaltered by bisulfite treatment, resulting in less biased uscfDNA methylation analysis. Using 5mCAdpBS-Seq, uscfDNA had lower levels of DNA methylation (∼15%) compared to mncfDNA and was enriched in promoters and CpG islands. Hypomethylated uscfDNA fragments were enriched in upstream transcription start sites (TSSs), and the intensity of enrichment was correlated with expressed genes of hemopoietic cells. Using tissue-of-origin deconvolution, we inferred that uscfDNA is derived primarily from eosinophils, neutrophils, and monocytes. As proof-of-principle, we show that characteristics of the methylation profile of uscfDNA can distinguish non-small cell lung carcinoma from non-cancer samples. The 5mCAdpBS-Seq workflow is recommended for any cfDNA methylation-based investigations.