bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune profiling of mouse lung adenocarcinoma paraffin tissues using multiplex immunofluorescence panel: a pilot study
Authors: Zhai Jie , Tamegnon Auriole , Jiang Mei , Pandurengan Renganayaki Krishna , Parra Edwin Roger
Published: June 2024

Background

Immune profiling has become an important tool for identifying predictive, prognostic and response biomarkers for immune checkpoint inhibitors from tumor microenvironment (TME). We aimed to build a multiplex immunofluorescence (mIF) panel to apply to formalin-fixed and paraffin-embedded tissues in mice tumors and to explore the programmed cell death protein 1/ programmed cell death 1 ligand 1 (PD-1/PD-L1) axis.

Results

An automated eight-color mIF panel was evaluated to study the TME using seven antibodies, including cytokeratin 19, CD3e, CD8a, CD4, PD-1, PD-L1, F4-80 and DAPI, then was applied in six mice lung adenocarcinoma samples. Cell phenotypes were quantified by software to explore the co-localization and spatial distribution between immune cells within the TME. This mice panel was successfully optimized and applied to a small cohort of mice lung adenocarcinoma cases. Image analysis showed a sparse degree of immune cell expression pattern in this cohort. From the spatial analysis we found that T cells and macrophages expressing PD-L1 were close to the malignant cells and other immune cells.

Conclusions

Comprehensive immune profiling using mIF in translational studies improves our ability to correlate the PD-1/PD-L1 axis and spatial distribution of lymphocytes and macrophages in mouse lung cancer cells to provide new cues for immunotherapy, that can be translated to human tumors for cancer intervention.
Antegrade long giant ileocolic intussusception via colon–cecum cancer lead points: case report with focus on the sign of the python colon
Authors: Pierro Antonio , Apollonio Biagio Francesco Pio , Mirco Paolo , Vallo Antonio , Cristino Roberto , Oriente Pierpaolo , Bevere Teresa , Testa Gianluca , Totaro Antonio
Published: June 2024

Background

Ileocolic intussusception is a rare condition that is difficult to diagnose. A pathological lead point, usually malignant, is often the cause of adult intussusception. In emergency scenarios, radiologists must be able to identify this entity and its causes and express their opinions on associated complications.

Case presentation

The hospital's emergency room admitted a 75-year-old woman who was suffering from intermittent abdominal pain and constipation. An abdominal contrast-enhanced computed tomography revealed a long giant ileocolic intussusception. Considering the clinical stability and the absence of signs of complications on CT, the patient did not undergo an urgent surgical procedure but underwent a colonoscopy the following day. Surprisingly, the colonoscopy highlighted the spontaneous resolution and revealed the presence of the three tumour lead points in the cecum and ascending colon. A CT was performed after the colonoscopy, confirming the intussusception's resolution. The surgeon performed a right oncological hemicolectomy. The malignant lead points on histological examination were moderate to poorly differentiated adenocarcinomas.

Conclusions

A giant and long ileocolic intussusception with a long embedded visceral segment (the python colon sign) could suggest pathological lead points in the cecum and ascending colon. Despite the large size, a spontaneous resolution of the python colon is possible. In this scenario, even if, on imaging, it is impossible to macroscopically identify a lead point, in cases of giant and long ileocolic intussusceptions, every effort must be undertaken to search for the cause of the intussusception.
Cervical and ocular vestibular-evoked myogenic potentials test results and its relation to vestibular signs and symptoms in individuals with vestibular migraine
Authors: Sanitha Adithya Sreedharan , Sinha Sujeet Kumar
Published: June 2024

Objective

The objective of the present study was to characterize the response rate, latency, and amplitude parameters of the cervical and ocular vestibular evoked myogenic potentials in individuals with vestibular migraine. The objective was also to describe the signs and symptoms exhibited by individuals with vestibular migraine and find out an association with VEMP results.

Method

Thirty individuals with a diagnosis of vestibular migraine and thirty healthy individuals participated in the study. The diagnosis of the vestibular migraine was made based on the diagnosis criteria given by the Barany Society and the International Headache Society. Cervical and ocular vestibular evoked myogenic potentials were recorded using 500 Hz tone burst stimulus for all the participants in both groups.

Results

The latency was prolonged, and the amplitude was reduced for both the cervical and ocular vestibular evoked myogenic potentials in individuals with vestibular migraine compared with healthy individuals. There was no association between signs and symptoms exhibited by vestibular migraine individuals and VEMP results.

Conclusions

Both the sacullocollic and otolith ocular pathways are affected in vestibular migraine. Hence, there is a necessity for vestibular evaluation in all patients with vestibular migraine to understand the spectrum of the pathology.
Evaluation of the tumor microenvironment in African American and non-Hispanic White patients with non-small cell lung cancer associated with PD-L1 expression or the presence of tertiary lymphoid structures.
Authors: Trendowski Matthew Raymond , Watza Donovan , Lusk Chrissy , Lonardo Fulvio , Ratliff Valerie , Wenzlaff Angela , Mamdani Hirva , Neslund-Dudas Christine , Boerner Julie , Schwartz Ann G. , Gibson Heather M
Published: June 2024

2627

Background: African Americans have higher incidence and mortality from lung cancer than non-Hispanic Whites, but investigations into differences in the tumor microenvironment and treatment response have been minimal. Due to the increasing utility of immunotherapy in the treatment of non-small cell lung cancer (NSCLC), we compared the immune cell composition and transcriptomic signature in the tumor microenvironment among African American and non-Hispanic White patients based on PD-L1 or tertiary lymphocyte structure (TLS) status to determine if there were differences of translational relevance. Methods: Using a cohort of 280 NSCLC patients from the INHALE study (non-Hispanic White: n = 155; African American: n = 125) with whole transcriptome microarray data, we determined the PD-L1 tumor proportion score (< 1% vs. ≥ 1%) and TLS status (presence/absence) within tumor tissue sections by immunohistochemistry. TLS were defined as dense aggregates of CD20 stained cells with a minimum diameter of 150 µm. Immune cell distribution within the tumor microenvironment was evaluated relative to differential gene expression. Results: Tumors from African Americans had a higher proportion of plasma cell signatures within the tumor microenvironment than tumors from non-Hispanic Whites. In addition, gene expression patterns in African American PD-L1 positive samples suggest these tumors contained significantly greater numbers of γδ T-cells and resting dendritic cells, along with fewer CD8+ T-cells compared to PD-L1 negative samples after adjusting for stage and histology. We also identified 22 genes that were differentially expressed between PD-L1 positive and negative tumors, along with 37 genes that were differentially expressed between TLS positive and negative tumors. Investigation of differential expression of B-cell/plasma cell related genes between the two patient populations revealed that four immunoglobulin genes in African Americans ( IGHA1, IGHD, IGKV2-29, and IGLL5) were associated with decreased mortality risk, while none of these genes were associated with overall survival in the non-Hispanic White population. Conclusions: In the first known race-stratified analysis of tumor microenvironment in lung cancer based on PD-L1 expression or TLS status, differences within the immune cell composition and transcriptomic signature were identified among non-Hispanic White and African American patients that may have therapeutic implications. Future investigation of these unique aspects within the tumor microenvironment will make advances in immunotherapy more equitable, thereby reducing the health disparities African Americans currently experience.
ctDNA as a biomarker in phase II study of tepotinib in advanced solid cancers with MET exon 14 skipping mutation or amplification (KCSG AL19-17).
Authors: Yang Yaewon , Kang Eun Joo , Lee Soohyeon , Kim Yu Jung , Lim Sun Min , Ahn Myung-Ju , Lee Youngjoo , Kim Tae Min , Kim Ilhwan , Ahn Hee Kyung , Lee Soonil , Oh So Yeon , Woo Kyun Bae , Ryu Hyewon , Park Kyong Hwa , Lee Ki Hyeong
Published: June 2024

3050

Background: Tepotinib consistently demonstrated antitumor activity in patients with MET exon 14 skipping mutation ( METex14) and promising activity in various cancers with MET amplification, according to previous reports. We assessed plasma ctDNA as a potential biomarker in MET-dysregulated advanced cancer patients with tepotinib treatment. Methods: KM-08 (KCSG AL19-17, NCT04647838) was a phase 2, multicenter study with tepotinib treatment for patients with advanced or metastatic solid cancers harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). For exploratory analyses, we analyzed the genetic profile using liquid-based NGS testing with AlphaLiquid-100 panel (IMBdx Inc. Seoul, KR) at baseline (T0), after six weeks during treatment (T1), and at the time of disease progression (T2). Results: Baseline ctDNA NGS data was available in 28 (80%) out of 35 patients enrolled in the trial. Among them, METex14 or MET amplification was detected in 18 patients, with a sensitivity of 64.3%. The most commonly co-mutated gene was TP53, followed b y PIK3CA, ATM, MYCN, and KRAS. The objective response rate (ORR) in plasma MET positive (PM+) patients was higher (81.2%) than the ORR in plasma MET negative (PM−) patients’ group (30.0%). In contrast, PM− group had a longer progression-free survival (PFS) and overall survival (OS) than PM+ group. PFS was 11.0 months (95% CI 8.1, 13.9) vs 6.0 months (95% CI 3.6, 8.3) and OS was NR vs 14.0 months (95% CI 4.7, 23.3), respectively. The molecular responder (MR, MET alteration variant allele frequency [VAF] T1/T0 <50%) was 80.0% (12/15 patients), and the molecular non-responder (MNR, METVAF T1/T0≥50%) was 20.0% (3/15 patients). ORR was higher in the MR group (91.7%) than in the MNR group (33.3%). PFS and OS were longer in the MR group than in the MNR group, 6.0 months (95% CI 0.0, 14.5) vs 3.0 months (95% CI 1.4, 4.6) with P= 0.114 and NR vs 4.0 months (95% CI 2.4, 5.6) with P= 0.067, respectively. Out of the 20 patients with samples available at T2, one had an on-target mutation on MET (D1228N, and Y1230H) while two had off-target emerging oncogenic alterations in KRAS, BRAF, and ERBB2 genes. Conclusions: In the liquid biomarker analysis in the MET-dysregulated cancer patients who were treated with tepotinib, the presence of ctDNA METalteration at baseline was associated with a higher response rate but shorter PFS and OS. The molecular response was well correlated with the radiological response and associated with better outcomes. (Funded by Merck KGaA, Darmstadt, Germany, ClinicalTrials.gov number, NCT04647838.) Clinical trial information: NCT04647838 .
Paired matched normal sequencing to accurately identify somatic clonal hematopoiesis mutations (CHm) in solid tumor tissue and plasma specimens.
Authors: Eterovic Karina , Batalini Felipe , Troxel Susan , Urban Brent , Harcar Mechelle , Shreeve Jacob , Ilsley Diane , Patel Ananddeep , Watters Matthew , Kutumbaka Kirthi , Sathyan Pratheesh , LoCoco Jennifer S. , Tierno Marni Brisson , Moss Tyler J
Published: June 2024

3051

Background: Clonal hematopoiesis (CH), characterized by the presence of somatic mutations in blood cells, can be found in cancer-related genes when sequencing tumor tissue or plasma samples. Inability to distinguish somatic, tumor-derived mutations from CHm can lead to inaccurate treatment decisions. In this prospective study, we confirmed potential CHm in solid tumors by sequencing and analysis of paired matched normal (PMN) specimens. Methods: We prospectively enrolled 56 patients diagnosed with advanced cancer, including lung (16), colorectal (13), breast (10), gastric (7), ovarian (2), pancreatic (2), liver (2), cervix (1), uterine (1), fallopian tube (1), and perihilar bile duct (1). Targeted next-generation sequencing using a 523 gene panel was performed on paired formalin-fixed paraffin-embedded (FFPE) and circulating tumor DNA (ctDNA) samples. Additionally, whole exome sequencing was performed on PMN buffy coat samples. Analysis of all three specimens was performed to classify somatic mutations as tumor-derived or CHm. Results: We identified 21 potential CHm within the FFPE and ctDNA samples of 13 patients (23.2% of the cohort) with lung (7), breast (2), liver (2), colorectal (1), and gastric (1) cancers. CHm were further confirmed when present in buffy coat samples. The VAF of CHm in FFPE and ctDNA samples exhibited a wide range, spanning from 0.85% to 38.4%, with 7 of those identified at <2% VAF. For these same aberrations, VAF in buffy coat samples ranged from 1.6% to 48%, with seven mutations exhibiting VAF levels <5%. Four of these CHm were classified as oncogenic or likely oncogenic. Four CHm, including an oncogenic TP53 mutation, were identified in the oldest patient (75 years old, lung cancer), while an oncogenic DNMT3A mutation was detected in the youngest patient (42 years old, breast cancer). Both had a 30-year history of smoking. Conclusions: Our findings identified somatic CHm in a substantial subset (23.2%) of solid tumors, with four identified as oncogenic or likely oncogenic mutations. The broad spectrum of VAFs for CHm suggests that using VAF as a cut-off to exclude likely CHm may be unreliable. The low VAF CHm found in matched normal specimens indicates low-pass sequencing may not detect critical CHm, even in paired analysis. The diverse age range of patients with CHm (42 to 75 years old) suggests that CHm are not restricted to older populations, and that additional factors, such as smoking history, may play a role. These findings underscore the importance of incorporating routine PMN buffy coat sequencing into clinical practice, to identify somatic CHm that can impact personalized cancer treatment strategies.
CUPCOMP: A multi-site UK trial in carcinoma of unknown primary: A comparison across tissue and liquid biomarkers.
Authors: Conway Alicia-Marie , Robinson Matthew , Concannon Matthew , Clive Sally , Tillett Tania , Shiu Kai-Keen , Medley Louise C. , Dasgupta Sonali , Ahmed Eliyaz , Warrington Kelly , Zair Zoulikha , Gillham Tess , Davis Aaron , Scott Julie-Anne , Taylor Alison , Stares Mark , Mitchell Claire , Oliveria Pedro , Burghel George , Cook Natalie
Published: June 2024

3059

Background: Cancer of Unknown Primary (CUP) is a difficult to treat cancer entity for which the tumour origins remain elusive. There is emerging evidence to support a precision medicine approach to aid treatment decisions, however scarcity of tumour tissue for molecular profiling remains a challenge. CUPCOMP sought to compare the feasibility of molecular profiling from both tissue and blood in patients (pts) diagnosed with CUP. Methods: A non-randomised prospective feasibility clinical trial conducted across 7 UK sites between 06/2021-02/2023. Eligible pts had a histological confirmed diagnosis of favourable/unfavourable CUP based on clinical, radiological, and pathological review at a CUP Multi-Disciplinary Team meeting and ESMO Guidelines for CUP. Pts had mutation profiling performed from circulating tumour DNA (ctDNA) (FoundationOne Liquid CDx) and tumour tissue (FoundationOne CDX or whole genome sequencing (WGS)). All results were discussed at a dedicated Molecular Tumour Board (MTB) to evaluate the activation state of oncogenic pathways. Results: Baseline characteristics of the 117 pts recruited are shown (Table). 114/117 (97%) pts had successful blood (109/117; 93% pts) or tissue (69/117; 59% pts) molecular profiling; both methods were performed in 64/117 (55%) pts. WGS was only successful in 15/21 pts where repeat biopsy was obtained. Where targeted tissue and blood profiling was performed using the same panel (49/117; 42%): 421/550 (77%) Single Nucleotide Variants (SNVs) found in tissue were concordant in ctDNA. ctDNA tumour fraction was ≥10% in 41/109 (35%) pts. In ctDNA, 1556 SNVs, across 271 genes, and 42 rearrangements were identified. 73/114 (64%) of cases carried an actionable alteration in blood or tissue, as determined by MTB. The most frequently reported actionable gene alterations were: KRAS (n=11; 10%); ATM (n=9; 8%); ARID1A (n=9; 8%); PIK3CA (n=10; 9%); NF2 (n=7; 6%); BRAF (n=7; 6%); FGFR2-fusion (n=7; 6%). A tumour mutational burden (TMB) of ≥10 mutations/Mb was detected in 25/117 (22%) of pts. Potential germline variants were found in 8% of pts. 80/114 (70%) pts were alive 6 months after consent to trial. Conclusions: Successful tissue-based molecular profiling is challenging in pts with CUP; achieved in only 59% of pts in this cohort. ctDNA analysis was feasible (93% successful) and reliably concordant with tissue. Potentially actionable alterations were found in 64% of pts. ctDNA molecular profiling should be considered as a reliable alternative to tissue-based testing in pts diagnosed with CUP. Clinical trial information: NCT04750109 . [Table: see text]
Non-invasive colorectal cancer detection using multimodal deep learning ensemble classifier.
Authors: Hong Seung Wook , Park Juntae , Lee Junnam , Ki Chang-Seok , Kim Dasom , Lee Tae-Rim , Ahn Jin Mo , Wang Mengchi , Carson Andrew , Lee Byung-In , Byeon Jeong-Sik , Cho Eunhae
Published: June 2024

3066

Background: The demand for alternative, non-invasive methods for colorectal cancer (CRC) screening is substantial. Cell-free DNA (cfDNA) whole genome sequencing (WGS) offers a promising avenue, utilizing diverse fragmentomic data. We aimed to develop a new approach: integrating fragment end motif by size (FEMS) with genomic coverage (COV) of cfDNA to enhance CRC screening. Methods: Participants were comprised of 1,506 colonoscopy verified normal samples, 130 advanced adenoma (AA) patients, 302 CRC patients (stage I: 28.5%, stage II: 25.5%, stage III: 31.1%, stage IV: 14.2%, unknown: 0.7%). We generated low depth cfDNA-WGS data (a minimum 40 million reads per sample) using the Novaseq 6000 sequencer. We minimized batch bias by normalizing with the same samples for each experimental batch. The development set comprised 1,332 samples (1,023 normal, 103 AA, and 206 CRC), while the validation set consisted of 606 samples (483 normal, 27 AA, and 96 CRC). Results: Our new algorithm achieved 84.0% sensitivity (95% CI: 81%-86%) for CRC and 69.9% (95% CI: 66%-81%) for AA in the development set, with a specificity of 90.0%. These findings were consistent in the external set with 84.9% specificity (95% CI: 82%-88%) and sensitivities of 80.2% (95% CI: 72%-88%) and 63.0% (95% CI: 44%-82%) for CRC and AA, respectively. The sensitivities across stages (Stage I: 80%, Stage II: 86.8%, Stage III: 78.8%, Stage IV: 96.7%) were similarly reflected in the validation sets (Stage I: 74%, Stage II: 83%, Stage III: 79%, Stage IV: 92%). Conclusions: Our multimodal deep learning model shows promise for accurate non-invasive colon cancer and AA detection using low-coverage cfDNA WGS. Its strong performance in detecting not only CRC but also AA lesions suggests its potential for early intervention and improved patient outcomes. The use of colonoscopy-verified normal samples strengthens the study's credibility and paves the way for future clinical translation.
Targeting rare variants of a pan-cancer target: The landscape of BRAF non-v600 mutations and BRAFfusions from 172,005 adult patients with cancer.
Authors: Coleman Niamh , Subbiah Vivek
Published: June 2024

3113

Background: BRAF is a recognized pan-cancer target, with dabrafenib in combination with trametinib receiving FDA accelerated approval for unresectable metastatic solid tumors with BRAF V600E mutation. BRAF fusions and mutations at codons aside from V600 (non-V600) activate the MAP kinase/ERK-signaling pathway, however the spectrum of these alterations is not yet well-defined. Preclinical data suggests that BRAF non-v600 mutations are diverse, with evidence of alternate signaling, requiring dimerization to function, while BRAFV600E tumors activate the pathway as monomers. We include a comprehensive analysis of non- BRAF V600 mutations and BRAF fusions in pan-cancer adult malignancies. Methods: 198,041 samples from 172,005 patients available from AACR Project GENIE v.15 (1) database were analyzed for the prevalence of non-V600 BRAF mutations, fusions and copy number alterations in a range of cancer types. Results: A total of 6374 separate non-V600 BRAF alterations were identified in 5876 samples (2.97%), including 1176 fusions (18.4%), 4435 missense mutations (69.6%), 299 truncating mutations (4.7%), and 245 in-frame mutations (3.8%), splice variants (3.4%). Most frequent tumors included lung (19%), melanoma (14%), colorectal (9.7%) glioma (5%), thyroid (1.4%). BRAF fusions were observed in 0.7% of tumor samples, most identified in glioma, prostate, lung, thyroid, and colorectal cancer (20%, 7.3%, 6.1%; 4%, 4% of identified BRAF fusions, respectively). Most fusions were considered driver events (1123, 95.5%); frequent fusion gene partners included KIAA1549, intragenic fusions, SND1, AGK, MKRN1 (39.9%, 15%, 4%, 3.3%, 2.4% of 1176 samples respectively). Of 4435 missense mutations identified, most were considered driver events (2734, 62%); 1701 missense mutations were variants of uncertain significance (VUS) using OncoKB database (38%). Missense mutations occurred across codons, most frequently involving codon 469 (n=584, 13.2%, G469A/V/R/E/S/L/K/I), 466 (n=310, 10.5%, G466V/E/A/R), 594 (n=506, 11.4%, D594G/N/A/E/H/Y/V/F), 601 (n=279, 6.3%, K601E/N/I/T/_S602delinsNT), 581 (n=231, 5.2%, N581S/I/Y/H/T/D/K) 597 (n=118; 2.7%, L597R/Q/S/V/P/H/I). BRAF amplification occurred in 0.14% of samples. Conclusions: While BRAF fusions are rare events across cancers, non-v600 BRAF alterations occur in 3% of malignancies. Atypical non-V600 BRAFalterations and BRAF fusions represent a distinct molecular cohort across cancers. Most BRAF fusion events and non-V600 missense mutations are characterized as oncogenic, underlining the spectrum of BRAF inhibition, and the urgent need to expand agents beyond the current BRAFV600 indications. Functional characterization of atypical BRAF variants is therefore crucial, together with enrolling patients with these rare alterations on rationally designed clinical trials. 1. Cancer Discov. 2017.
Efficacy and safety of CalliSpheres drug-eluting beads for bronchial arterial chemoembolization combined with intravenous chemotherapy for extensive-stage small cell lung cancer.
Authors: Cai Daxia , Tu Jianfei , Wang Yonghui
Published: June 2024

e20137

Background: We aim to explore the efficacy and tolerability of Drug-Eluting Bead Bronchial Arterial Chemotherapy Embolization (DEB-BACE) combined with intravenous chemotherapy in the treatment of patients with initially diagnosed extensive-stage small cell lung cancer (SCLC). Methods: We collected data from 24 patients with extensive-stage small cell lung cancer who received DEB-BACE combined with intravenous chemotherapy (DEB-BACE-V) and initially diagnosed at our hospital between 2013 and 2022. Among them, nine patients received BACE combined with intravenous chemotherapy from the first-line (first-line DEB-BACE-V), ten patients from the third-line (third -line DEB-BACE-V), and five patients from the second-line (second -line DEB-BACE-V). Then, the treatment response (objective response rate and rate of cancer regression) and tumor marker levels were evaluated at the first month and third month after treatment. The quality of life was assessed using the EORTC QLQ-C30 scale. Overall survival (OS) was also evaluated. First, compare the first-line DEB-BACE-V group with the second-line DEB-BACE-V group. Then, compare the first-line DEB-BACE-V group with third-line DEB-BACE-V group. Lastly, compare the second-line DEB-BACE-V group with the third-line DEB-BACE-V group. Results: In initially diagnosed extensive-stage SCLC patients treated with DEB-BACE combined with intravenous chemotherapy, first and third month post treatment, the objective response rates were 58.33% and 79.17%, respectively; and the rates of cancer regression were 75% and 91.67%, respectively. In addition, the neuron-specific enolase (NSE) and progastrin-releasing peptide levels were reduced at the third and sixth month. Quality of life assessed by EORTC QLQ-C30 scale, which included subscales of general health status, functional domains, symptom domains, and single domains except for financial difficulty, was markedly improved in first and third month of post treatment. Adverse reactions were mild and manageable, the most common being chest pain and low fever. Median values of OS in first-line DEB-BACE-V, second -line DEB-BACE-V and third -line DEB-BACE-V were 15.7 (95% CI: 9.1595-20.759) months, 29.63 (95% CI: 20.5684-36.268) months 16.92 (95% CI: 10.4044-21.871) months, and respectively. Conclusions: Due to its favorable therapeutic response, quality of life, survival benefits, and safety profile, DEB-BACE combined with intravenous chemotherapy may become a treatment option for patients with extensive-stage SCLC, particularly as second-line therapy.
“Women Work Particularly Well in Community Organizations”
Authors: Plutshack Victoria , Merck Ashton
Published: June 2024

From 1939 to 1941, the US Rural Electrification Administration conducted a nationwide educational campaign to share the benefits of electricity with rural Americans, known as the Electric Farm Equipment Show. A key part of the show was a series of appliance schools, which were run by female home economists and designed for a female audience. This article examines an appliance school organized for one REA women's club and the efforts of officials like REA chief home electrification specialist Clara O. Nale to navigate the disconnect between the official REA project, which assumed a gendered division of labor, and the real needs of the farm women they served. Through the Comanche County REA Women's Club, the article explores how REA administrators imagined that women would participate in its cooperative-led electrification efforts, women's engagement with and resistance to the REA's programming, and how technology adoption was ultimately mediated through women's priorities.
Long-Term Resistance Trained Human Muscles Have More Fibers, More Myofibrils, and Tighter Myofilament Packing Than Untrained
Authors: MAEO SUMIAKI , BALSHAW THOMAS G. , MÄRZ BENJAMIN , ZHOU ZHAOXIA , HAUG BILL , MARTIN NEIL R. W. , MAFFULLI NICOLA , FOLLAND JONATHAN P.
Published: June 2024

Introduction

Increases in skeletal muscle size occur in response to prolonged exposure to resistance training that is typically ascribed to increased muscle fiber size. Whether muscle fiber number also changes remains controversial, and a paucity of data exists about myofibrillar structure. This cross-sectional study compared muscle fiber and myofibril characteristics in long-term resistance-trained (LRT) versus untrained (UNT) individuals.

Methods

The maximal anatomical cross-sectional area (ACSAmax) of the biceps brachii muscle was measured by magnetic resonance imaging in 16 LRT (5.9 ± 3.5 yr’ experience) and 13 UNT males. A muscle biopsy was taken from the biceps brachii to measure muscle fiber area, myofibril area, and myosin spacing. Muscle fiber number, and myofibril number in total and per fiber were estimated by dividing ACSAmax by muscle fiber area or myofibril area, and muscle fiber area by myofibril area, respectively.

Results

Compared with UNT, LRT individuals had greater ACSAmax (+70%, P < 0.001), fiber area (+29%, P = 0.028), fiber number (+34%, P = 0.013), and myofibril number per fiber (+49%, P = 0.034) and in total (+105%, P < 0.001). LRT individuals also had smaller myosin spacing (−7%, P = 0.004; i.e., greater packing density) and a tendency toward smaller myofibril area (−16%, P = 0.074). ACSAmax was positively correlated with fiber area (r = 0.526), fiber number (r = 0.445), and myofibril number (in total r = 0.873 and per fiber r = 0.566), and negatively correlated with myofibril area (r = −0.456) and myosin spacing (r = −0.382) (all P < 0.05).

Conclusions

The larger muscles of LRT individuals exhibited more fibers in cross-section and larger muscle fibers, which contained substantially more total myofibrils and more packed myofilaments than UNT participants, suggesting plasticity of muscle ultrastructure.
Σχεδιασμός και ανάπτυξη φορητών σοβαρών παιχνιδιών επαυξημένης πραγματικότητας με βάση τον χάρτη και μελέτη της επίδρασης της χρήσης τους στην ανάπτυξη της χωρικής ικανότητας
Authors: Μαρκούζης Δημήτριος
Published: June 2024

Ο προσανατολισμός και η μετακίνηση στο χώρο έχουν καθοριστική σημασία για τον άνθρωπο. O άνθρωπος, μετακινείται καθημερινά σε γνωστές και άγνωστες διαδρομές στις οποίες χρησιμοποιεί χωρικές πληροφορίες, είτε ανακαλώντας αυτές από τη μνήμη του είτε αποκωδικοποιώντας λεκτικές οδηγίες ή συμβολικά μέσα π.χ. χάρτες. Η ανάπτυξη της χωρικής ικανότητας των νηπίων, έχει σημαντικές θετικές συνέπειες για την γνωστική τους ανάπτυξη γενικότερα και τις μελλοντικές επιδόσεις τους στα πεδία των θετικών και των θεωρητικών επιστημών. Παρόλα αυτά, ο χωρικός προσανατολισμός στα Αναλυτικά Προγράμματα Σπουδών του Νηπιαγωγείου αρκετών χωρών προσεγγίζεται μέσω της Γεωμετρίας, δίνοντας μικρή σημασία στη χρήση των χαρτών, ενώ, οι απουσιάζει από αυτά η χρήση φορητών Ψηφιακών Τεχνολογιών που συνάδουν με την εν κινήσει μάθηση και την εγκαθιδρυμένη προσέγγιση της γνώσης. Από την άλλη πλευρά τα τελευταία χρόνια αυξάνεται η συνεχώς η υπολογιστική ισχύς φορητών συσκευών, όπως είναι κινητά τηλέφωνα και ταμπλέτες. Μια από τις τεχνολογίες αιχμής που χρησιμοποιούν οι συσκευές αυτές είναι και η επαυξημένη πραγματικότητα, η οποία αξιοποιεί την αυτόματη εύρεση της τοποθεσίας του χρήστη προβάλλοντας του εξατομικευμένες πληροφορίες στην οθόνη της συσκευής του ανάλογα με τις επιλογές του (πχ μετακίνηση στο χώρο). Η επαυξημένη πραγματικότητα είναι δυνατόν να ενταχθεί σε διάφορες εφαρμογές φορητών συσκευών, μεταξύ των οποίων είναι και τα ψηφιακά παιχνίδια, που έχουν σχεδιαστεί για ψυχαγωγία και σε λιγότερα τα οποία χρησιμοποιούν την τεχνολογία αυτή για μαθησιακούς σκοπούς. Τα παιχνίδια αυτά που έχουν ως αποκλειστικό σκοπό την εκπαίδευση αναφέρονται στη βιβλιογραφία ως σοβαρά παιχνίδια. Στην παρούσα διατριβή σχεδιάστηκαν σοβαρά παιχνίδια επαυξημένης πραγματικότητάς, με βάση το χάρτη για φορητές συσκευές και μελετήθηκε επίδραση της χρήσης τους στην ανάπτυξη της χωρικής ικανότητας των νήπιων. Η γενική δομή της διατριβής έχει ως εξής. Αρχικά, μελετάται το θεωρητικό πλαίσιο γύρω από το παιχνίδι και την επαυξημένη πραγματικότητα. Έπειτα, πραγματοποιείται βιβλιογραφική ανασκόπηση αναφορικά με το αναπτυξιακό μοντέλο, που επικρατεί σήμερα για την ανάπτυξη της χωρικής ικανότητας των νηπίων και της χρήσης του χάρτη αλλά και με το κατά πόσο νέες τεχνολογίες χρησιμοποιούνται προς αυτήν την κατεύθυνση. Την καταγραφή της υπάρχουσας κατάστασης ακολουθεί η προβληματική και η περιγραφή των ερευνητικών δραστηριοτήτων και των εφαρμογών επαυξημένης πραγματικότητας που σχεδιάστηκαν. Κατόπιν γίνεται ποσοτική και ποιοτική μελέτη των αποτελεσμάτων των δραστηριοτήτων και τέλος πραγματοποιείται συζήτηση πάνω στα αποτελέσματα και προτείνονται μελλοντικές επεκτάσεις. H παρούσα διατριβή φιλοδοξεί να συνεισφέρει μελετώντας το κατά πόσο δραστηριότητες βασισμένες σε σύγχρονες ψηφιακές τεχνολογίες, όπως οι φορητές υπολογιστικές συσκευές και η επαυξημένη πραγματικότητα, μπορούν να επηρεάσουν το αναπτυξιακό μοντέλο σχετικά με τη χωρική σκέψη και την ανάγνωση και χρήση χάρτη.
Comparative observational study on diagnostic utility of impulse oscillometry vs spirometry in obstructive airway diseases
Authors: Sarkar Souvik , Jadhav Ulhas
Published: June 2024

Background Obstructive airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma, pose significant global health challenges. Early and accurate diagnosis is crucial for effective management. Although Spirometry has traditionally been the cornerstone of diagnostics, Impulse Oscillometry (IOS) has emerged as a promising alternative. This study aims to compare the diagnostic performance of Spirometry and IOS in patients attending the Respiratory Medicine Department at the Acharya Vinoba Bhave Rural Hospital, Sawangi, India. Methods A Comparative Observational Study was conducted between August 2022 and August 2024, enrolling patients who met specific inclusion criteria. Data were collected through a comprehensive medical history, clinical examination, routine blood tests, chest radiography, High-resolution computed tomography (HRCT), spirometry, and IOS. Key parameters, including Forced expiratory volume in the first second FEV1, FEV1/FVC (Forced Expiratory Volume), (Forced Expiratory Volume) FVC, (Forced Expiratory Flow) FEF 25-75 for Spirometry, and R5, R20, fres, X5, and AX for IOS, were analyzed using the Chi-Square Test and Student’s t-test with SPSS 27.0 and GraphPad Prism 7.0. Expected outcome The study included 130 participants with the primary objective of evaluating IOS’s diagnostic advantages of IOS over spirometry. Our findings demonstrate that IOS offers enhanced sensitivity for diagnosing early small airway diseases, which is a crucial factor for early diagnosis in both pediatric and adult populations.
Routing and Staffing in Customer Service Chat Systems with Generally Distributed Service and Patience Times
Authors: Long Zhenghua , Tezcan Tolga , Zhang Jiheng
Published: June 2024

Problem definition: We study customer service chat (CSC) systems, in which agents can serve multiple customers simultaneously, with generally distributed service and patience times. The multitasking capability of agents introduces idiosyncratic challenges when making routing and staffing decisions. Methodology/results: To determine the dynamic matching of arriving customers with available agents, we first formulate a routing linear program (LP) based on system primitives. Inspired by the optimal solution of the routing LP, we design a parsimonious dynamic routing policy that is independent of arrival rate and service capacity information. We also use the optimal solution to develop closed-form approximations for crucial performance metrics and show that a similar LP can be utilized to make staffing decisions. Through extensive simulation experiments, we showcase the efficacy of our approximations and staffing decisions. Furthermore, under our proposed policy, the CSC system exhibits a unique stationary fluid model in which the steady-state performance measures align with our approximations. Managerial implications: The extant literature primarily focuses on Markovian systems with exponential distributions. In this paper, customers’ service and patience times are allowed to be generally distributed to agree with practical settings. Our findings indicate that the distributions have a significant impact on routing policies, staffing decisions, and system performance.

Funding: Z. Long was supported by the National Natural Science Foundation of China [Grants 72101112, 72132005, and 72271119] and Jiangsu Province, China [Grant BK20210171]. J. Zhang was supported by the Hong Kong Research Grants Council, General Research Fund [Grants 16208120 and 16214121].

Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.0114 .
Interconnection, NIS2 and the mobile device
Authors: Becenti Monique
Published: June 2024

NIS2 will soon come into force all over the EU and – much like the GDPR – it threatens large fines for those that don’t comply. However, it may serve as a much-needed wake up call for those who are overlooking the fastest-growing part of their attack surface – the mobile device.
Enhancing network resilience against growing cyberthreats
Authors: Walsh Brendan
Published: June 2024

Networks are becoming ever-more complex, and people with the right skills to manage them securely are in desperately short supply. However, with the right network management environment – one that supports automation and operational efficiency – supported by relevant training, you can make your networks more resilient to current and future threats.
Is new legislation the answer to curbing cybercrime?
Authors: Lomba Vincent
Published: June 2024

Cyber attacks are on the increase, in terms of both the number of attacks and the damage they cause. Encouraging organisations to improve their cyber security has had only a limited effect. Now it’s the turn of legislation and regulation, with the Cyber Resilience Act (CRA) and Network and Information Security Directive (NIS2) coming into force in the EU. But what kind of impact are they likely to have?
OS PROBLEMAS ESTRUTURAIS QUE IMPACTAM AS AULAS DE EDUCAÇÃO FÍSICA NAS ESCOLAS PÚBLICAS
Authors: Bispo dos Santos Paulo Victor , Nascimento Pereira Ana Carolina , Alves Nogueira Souza Suzana
Published: June 2024

Este estudo tem como objetivo analisar quais são os problemas estruturais mais marcantes e presentes nas escolas públicas e que impactam a organização do trabalho pedagógico nas aulas de Educação Física, para que, dessa forma, seja possível  contribuir com as discussões acerca de reformulação de novas propostas nas escolas. A partir de uma revisão bibiográfica, de caráter descritivo e abordagem qualitativa, discute-se aqui, como as questões estruturais são vistas pelos professores de Educação Física das escolas públicas e quais desdobramentos e possibilidades aparecem ou têm que aparecer nessas circunstâncias, visto que a evasão desses contextos contribui com a disseminação de uma perspectiva   pejorativa   quanto   à  Educação Física  como componente curricular. Foi evidenciada também a importância da promoção de uma mobilização social do corpo docente em vista de atingir melhores parâmetros estruturais. As dificuldades estruturais estão presente na maioria das escolas públicas, elas são um fator limitante para a práxis qualificada; entretanto, não devem ser vistas como um pretexto para abdicar do ensino de qualidade.
Development of donor specific antibodies after SARS-CoV-2 vaccination: What do we know so far?
Authors: Daoud Ahmed , Soliman Karim , Posadas Salas Maria Aurora , Vaishnav Sakshi , Uehara Genta , Abdelkader Ahmed , Fulop Tibor , Casey Michael J
Published: June 2024

Vaccination against Coronavirus disease-19 (COVID-19) was pivotal to limit spread, morbidity and mortality. Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies (DSAs) or increase in mean fluorescence intensity (MFI) of pre-existing DSAs in kidney transplant recipients (KTRs). This study involved a detailed literature search through December 2nd, 2023 using PubMed as the primary database. The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords: "COVID-19", "SARS-CoV-2 Vaccination", "Kidney, Renal Transplant", and "Donor specific antibodies". The results from related studies were collated and analyzed. A total of 6 studies were identified, encompassing 460 KTRs vaccinated against COVID-19. Immunological responses were detected in 8 KTRs of which 5 had increased MFIs, 1 had de novo DSA, and 2 were categorized as either having de novo DSA or increased MFI. There were 48 KTRs with pre-existing DSAs prior to vaccination, but one study (Massa et al ) did not report whether pre-existing DSAs were associated with post vaccination outcomes. Of the remaining 5 studies, 35 KTRs with pre-existing DSAs were identified of which 7 KTRs (20%) developed de novo DSAs or increased MFIs. Overall, no immunological response was detected in 452 (98.3%) KTRs. Our study affirms prior reports that COVID-19 vaccination is safe for KTRs, especially if there are no pre-existing DSAs. However, if KTRs have pre-existing DSAs, then an increased immunological risk may be present. These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.
Two Very Rare Case of Simultaneous Bilateral Intertrochanteric Fracture Operated in Single Stage – A Case Report
Authors:   Department of Orthopedics, Manipal Tata Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India,, Kumar Sachin , Thakur Rajesh ,   Department of Joint Replacement and Orthopedics, Tata Main Hospital, Jamshedpur, Jharkhand, India., Mane Akash ,   Department of Orthopedics, Manipal Tata Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India,, Wooly Sameer ,   Department of Orthopedics, Manipal Tata Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India,, Sarkar Somit ,   Department of Joint Replacement and Orthopedics, Tata Main Hospital, Jamshedpur, Jharkhand, India.
Published: June 2024

Introduction: Unilateral intertrochanteric fractures are common injuries in elderly population. Simultaneous bilateral intertrochanteric fractures do occur but are very rare and only a few cases have been reported in the literature. Case Report: We report two cases with different modes of injury. Both cases were fixed in a single stage by proximal femoral nailing (PFN). The first case had multiple comorbidities and after 6 weeks of follow up, she suddenly expired at home due to medical issue. The second case is the only case reported with associated bilateral superior and inferior pubic rami fracture. PFN was done in a single stage and at 1-year follow-up, the patient was having a good functional outcome. Conclusion: Simultaneous bilateral intertrochanteric fractures are very rare injuries but these are potentially life-threatening with high morbidity. Quick assessment and early single-stage stabilization with proximal femoral nail give stable fixation and good functional outcome. Keywords: Bilateral intertrochanteric fracture, proximal femoral nailing, pubic rami.
"Four Corners and a Void": Idiocy and Childhood Disability in Nineteenth-Century America
Authors: Irving Kathryn
Published: June 2024

abstract: Over the second half of the nineteenth century, thousands of Americans were admitted to schools for so-called idiotic children, later known as institutions for the feebleminded and linked to the Eugenics movement. While idiocy is often presumed to be the antecedent of intellectual disability, an analysis of the stories of three hundred children admitted to one such institution over a forty-year period demonstrates an unexpected diversity of appearances, abilities, and behaviors. Within the walls of the institution, idiocy was composed of children whose perceived abilities deviated from the expectations of their social position. Families further shaped the diagnosis of idiocy by negotiating the timing of admission for their children, influenced not only by personal factors, but by shifting educational and employment opportunities, and cultural tolerance of diversity. Consequently, idiocy became the broadest descriptor of disability during the nineteenth century.
Phase retrieval via conjugate gradient minimization in double-plane lensless holographic microscopy
Authors: Winnik Julianna , Suski Damian , Arcab Piotr , Rogalski Mikołaj , Trusiak Maciej
Published: June 2024

Optimization-based phase retrieval method for digital lensless holographic microscopy in the double-plane recording configuration is proposed. In our method the phase retrieval is framed as an optimization problem that can be efficiently and rigorously tackled with gradient decent tools. This is done with the conjugate gradient method that possesses excellent theoretical features such as global and fast convergence (compared to steepest descent) and relatively low computational cost (compared to second order optimizers). The proposed method is extensively tested with simulations and experimental measurements that show superiority of our method over the Gerchberg-Saxton algorithm, especially in terms of reconstruction of problematic low frequency components of viable phase information.
Terahertz absorption properties of different graphene layers based on the Salisbury effect
Authors: Hou Liuyu , Bi Kaixi , Li Qiannan , Zhang Shengguo , Guo Miaoli , Zhuang Yan , Huang Donghui , Zhang Shuai , Han Shuqi , Mei Linyu
Published: June 2024

Terahertz (THz) absorbers based on the Salisbury screen have attracted significant attention for high absorption performance and simple structure. Graphene is suitable for high-performance THz absorbers due to its extraordinary electronic and optical properties. The study of graphene THz absorbers based on Salisbury screens has attracted great interest, where the number of graphene layers significantly affects the interface impedance matching and absorption efficiency. In this work, we proposed a sandwich-structured graphene/Polyimide (PI) /Au THz absorber based on the Salisbury screen. The results show that the absorption peak tended to increase and then decrease with the increase in the number of graphene layers. The simulation demonstrates that the real and imaginary parts of the relative impedance of the 3-5 layer graphene absorber were 1.02 and 0.01, which achieved a better impedance matching with the free space. Meanwhile, the measured sheet resistance value of 426 Ω/sq was closest to the free-space impedance value of 377 Ω, consistent with the simulation results. The corresponding absorption reached a maximum value of 98.7% at 0.82 THz (measured). In addition, the absorption peak decreased from 98.7% to 86.7% as the angle of incidence increased from 0° to 60°. This demonstrates the advantage of wide-angle absorption. The proposed device is suitable for applications in electromagnetic shielding and imaging, while the suggested method can be employed for the fabrication of other graphene-based devices.
Aberration aware feature detection and description
Authors: Chen Bingkun , Zhou Jinwen , Li Menghao , Xu Hao , Feng Huajun , Chen Yueting
Published: June 2024

Feature detection and description are crucial for image matching, as better performance at this stage leads to more accurate matching results, which is essential for subsequent vision-based tasks. However, images captured by different optical systems may suffer from various optical aberrations, especially in off-axis field and out-of-depth-of-field regions, making it challenging for models to extract consistent feature locations and descriptors. In this paper, we propose what we believe to be a novel method for training feature detection and description networks by incorporating optical system aberrations modeled by point spread function(PSF). We introduce PSF augmentation and homographic PSF adaptation, which customize the training of feature detection and description models for specific optical systems using general unlabeled image datasets. Experimental results demonstrate that our method significantly improves the performance of feature detection and description in images captured by given cameras.