bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the delivery costs of COVID-19 vaccination using the COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool: the Lao People’s Democratic Republic experience
Authors: Yeung Karene Hoi Ting , Kim Eunkyoung , Yap Wei Aun , Pathammavong Chansay , Franzel Lauren , Park Yu Lee , Cowley Peter , Griffiths Ulla Kou , Hutubessy Raymond Christiaan W.
Published: July 2023

Background

The COVID-19 Vaccine Introduction and deployment Costing (CVIC) tool was developed to assist countries to estimate incremental financial costs to roll out COVID-19 vaccines. This article describes the purposes, assumptions and methods used in the CVIC tool and presents the estimated financial costs of delivering COVID-19 vaccines in the Lao People’s Democratic Republic (Lao PDR).

Methods

From March to September 2021, a multidisciplinary team in Lao PDR was involved in the costing exercise of the National Deployment and Vaccination Plan for COVID-19 vaccines to develop potential scenarios and gather inputs using the CVIC tool. Financial costs of introducing COVID-19 vaccines for 3 years from 2021 to 2023 were projected from the government perspective. All costs were collected in 2021 Lao Kip and presented in United States dollar.

Results

From 2021 to 2023, the financial cost required to vaccinate all adults in Lao PDR with primary series of COVID-19 vaccines (1 dose for Ad26.COV2.S (recombinant) vaccine and 2 doses for the other vaccine products) is estimated to be US$6.44 million (excluding vaccine costs) and additionally US$1.44 million and US$1.62 million to include teenagers and children, respectively. These translate to financial costs of US$0.79–0.81 per dose, which decrease to US$0.6 when two boosters are introduced to the population. Capital and operational cold-chain costs contributed 15–34% and 15–24% of the total costs in all scenarios, respectively. 17–26% went to data management, monitoring and evaluation, and oversight, and 13–22% to vaccine delivery.

Conclusions

With the CVIC tool, costs of five scenarios were estimated with different target population and booster dose use. These facilitated Lao PDR to refine their strategic planning for COVID-19 vaccine rollout and to decide on the level of external resources needed to mobilize and support outreach services. The results may further inform inputs in cost-effectiveness or cost–benefit analyses and potentially be applied and adjusted in similar low- and middle-income settings.
TREC mediated oncogenesis in human immature T lymphoid malignancies preferentially involves ZFP36L2
Authors: Balducci Estelle , Steimlé Thomas , Smith Charlotte , Villarese Patrick , Feroul Mélanie , Payet-Bornet Dominique , Kaltenbach Sophie , Couronné Lucile , Lhermitte Ludovic , Touzart Aurore , Dourthe Marie-Emilie , Simonin Mathieu , Baruchel André , Dombret Hervé , Ifrah Norbert , Boissel Nicolas , Nadel Bertrand , Macintyre Elizabeth , Cieslak Agata , Asnafi Vahid
Published: July 2023

The reintegration of excised signal joints resulting from human V(D)J recombination was described as a potent source of genomic instability in human lymphoid cancers. However, such molecular events have not been recurrently reported in clinical patient lymphoma/leukemia samples. Using a specifically designed NGS-capture pipeline, we here demonstrated the reintegration of T-cell receptor excision circles (TRECs) in 20/1533 (1.3%) patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL). Remarkably, the reintegration of TREC recurrently targeted the tumor suppressor gene, ZFP36L2, in 17/20 samples. Thus, our data identified a new and hardly detectable mechanism of gene deregulation in lymphoid cancers providing new insights in human oncogenesis.
A novel interface between the N-terminal and coiled-coil domain of STAT1 functions in an auto-inhibitory manner
Authors: Remling Linus , Gregus Anke , Wirths Oliver , Meyer Thomas , Staab Julia
Published: July 2023

Background

STAT1 is an intracellular signaling molecule that is crucially involved in the regulation of the innate immune system by activation of defense mechanisms against microbial pathogens. Phosphorylation-dependent activation of the STAT1 transcription factor is associated with a conversion from an antiparallel to parallel dimer configuration, which after nuclear import binds to DNA. However, not much is known about the specific intermolecular interactions that stabilize unphosphorylated, antiparallel STAT1 complexes prior to activation.

Results

In this study, we identified a previously unknown interdimeric interaction site, which is involved in the termination of STAT1 signaling. Introduction of the glutamic acid-to-alanine point mutation E169A in the coiled-coil domain (CCD) by site-directed mutagenesis led to increased tyrosine phosphorylation as well as accelerated and prolonged nuclear accumulation in transiently transfected cells. In addition, DNA-binding affinity and transcriptional activity were strongly enhanced in the substitution mutant compared to the wild-type (WT) protein. Furthermore, we have demonstrated that the E169 residue in the CCD mediates the release of the dimer from the DNA in an auto-inhibitory manner.

Conclusion

Based on these findings, we propose a novel mechanism for the inactivation of the STAT1 signaling pathway, assigning the interface with the glutamic acid residue 169 in the CCD a crucial role in this process.
ATP purinergic receptor signalling promotes Sca-1+ cell proliferation and migration for vascular remodelling
Authors: Cui Yiqin , Li Chunshu , Zeng Xinyi , Wei Xiaoyu , Li Pengyun , Cheng Jun , Xu Qingbo , Yang Yan
Published: July 2023

Aims

Vascular resident stem cells expressing stem cell antigen-1 (Sca-1+ cells) promote vascular regeneration and remodelling following injury through migration, proliferation and differentiation. The aim of this study was to examine the contributions of ATP signalling through purinergic receptor type 2 (P2R) isoforms in promoting Sca-1+ cell migration and proliferation after vascular injury and to elucidate the main downstream signalling pathways.

Methods and results

ATP-evoked changes in isolated Sca-1+ cell migration were examined by transwell assays, proliferation by viable cell counting assays and intracellular Ca2+ signalling by fluorometry, while receptor subtype contributions and downstream signals were examined by pharmacological or genetic inhibition, immunofluorescence, Western blotting and quantitative RT-PCR. These mechanisms were further examined in mice harbouring TdTomato-labelled Sca-1+ cells with and without Sca-1+-targeted P2R knockout following femoral artery guidewire injury. Stimulation with ATP promoted cultured Sca-1+ cell migration, induced intracellular free calcium elevations primarily via P2Y2R stimulation and accelerated proliferation mainly via P2Y6R stimulation. Enhanced migration was inhibited by the ERK blocker PD98059 or P2Y2R-shRNA, while enhanced proliferation was inhibited by the P38 inhibitor SB203580. Femoral artery guidewire injury of the neointima increased the number of TdTomato-labelled Sca-1+ cells, neointimal area and the ratio of neointimal area to media area at 3 weeks post-injury, and all of these responses were reduced by P2Y2R knockdown.

Conclusions

ATP induces Sca-1+ cell migration through the P2Y2R–Ca2+–ERK signalling pathway, and enhances proliferation through the P2Y6R–P38-MAPK signalling pathway. Both pathways are essential for vascular remodelling following injury.
The role of TET2-mediated ROBO4 hypomethylation in the development of diabetic retinopathy
Authors: Zhao Liangliang , Xu Haitao , Liu Xin , Cheng Yan , Xie Jia’nan
Published: July 2023

Background

In diabetic retinopathy, increasing evidence points to a link between the pathogenesis of retinal microangiopathy and the endothelial cell-specific factor roundabout4 (ROBO4). According to earlier research, specificity protein 1 (SP1) enhances the binding to the ROBO4 promoter, increasing Robo4 expression and hastening the progression of diabetic retinopathy. To determine if this is related to aberrant epigenetic modifications of ROBO4, we examined the methylation level of the ROBO4 promoter and the corresponding regulatory mechanism during the course of diabetic retinopathy and explored the effect of this mechanism on retinal vascular leakage and neovascularization.

Methods

The methylation level of CpG sites in the ROBO4 promoter was detected in human retinal endothelial cells (HRECs) cultured under hyperglycemic conditions and retinas from streptozotocin-induced diabetic mice. The effects of hyperglycemia on DNA methyltransferase 1, Tet methylcytosine dioxygenase 2 (TET2), 5-methylcytosine, 5-hydroxymethylcytosine, and the binding of TET2 and SP1 to the ROBO4 promoter, as well as the expression of ROBO4, zonula occludens 1 (ZO-1) and occludin were examined. Short hairpin RNA was used to suppress the expression of TET2 or ROBO4 and the structural and functional changes in the retinal microvascular system were assessed.

Results

In HRECs cultured under hyperglycemic conditions, the ROBO4 promoter methylation level decreased. Hyperglycemia-induced TET2 overexpression caused active demethylation of ROBO4 by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, which enhanced the binding of SP1 to ROBO4, increased the expression of ROBO4, and decreased the expression of ZO-1 and occludin, leading to the abnormalities in monolayer permeability, migratory ability and angiogenesis of HRECs. The above pathway was also demonstrated in the retinas of diabetic mice, which caused leakage from retinal capillaries and neovascularization. Inhibition of TET2 or ROBO4 expression significantly ameliorated the dysfunction of HRECs and retinal vascular abnormalities.

Conclusions

In diabetes, TET2 can regulate the expression of ROBO4 and its downstream proteins by mediating active demethylation of the ROBO4 promoter, which accelerates the development of retinal vasculopathy. These findings suggest that TET2-induced ROBO4 hypomethylation is a potential therapeutic target, and anti- TET2/ROBO4 therapy is anticipated to emerge as a novel strategy for early intervention and delayed progression of diabetic retinopathy.
Reticular fibre structure in the differential diagnosis of parathyroid neoplasms
Authors: Hu Xiumei , He Shurong , Jiang Xingran , Wei Ping , Zhou Xiang , Shi Zhongyue , Li Xue , Lu Jun , Zhao Hongying , Wei Bojun , Jin Mulan
Published: July 2023

Background

To investigate the characteristics of reticular fibre structure (RFS) in parathyroid adenoma (PTA), atypical parathyroid tumour (APT), and parathyroid carcinoma (PTC), and to assess its value as a diagnostic indicator.

Methods

Clinical data and pathological specimens of patients with PTA, APT or PTC were collected. Reticular fibre staining was performed to observe the characteristics of RFS. This study evaluated the incidence of RFS destruction in parathyroid tumours, compared RFS destruction between primary PTC and recurrent and metastatic PTC, and explored the association between RFS destruction and clinicopathological features of APT and primary PTC.

Results

Reticular fibre staining was performed in 50 patients with PTA, 25 patients with APT, and 36 patients with PTC. In PTA cases, a delicate RFS was observed. In both the APT and PTC groups, incomplete RFS areas were observed. The incidence of RFS destruction was different among the PTA, APT, and PTC groups (P < 0.001, χ2-test), at 0% (0/50), 44% (11/25), and 86% (31/36), respectively. When differentiating PTC from APT, the sensitivity and specificity of RFS destruction were 81% and 56%, respectively. The incidence of RFS destruction was 73% (8/11) in the primary PTC group and 92% (23/25) in the recurrent and metastatic PTC groups. In both the APT group and primary PTC group, no correlation was found between RFS destruction and clinicopathological features.

Conclusion

RFS destruction may indicate that parathyroid tumours have unfavourable biological behaviours.Reticular fibre staining may be a valuable tool for improving the diagnostic accuracy in parathyroid tumours.
Dynamic alteration of intrinsic properties of the cerebellar Purkinje cell during the motor memory consolidation
Authors: Jang Dong Cheol , Chung Geehoon , Kim Sun Kwang , Kim Sang Jeong
Published: July 2023

Intrinsic plasticity of the cerebellar Purkinje cell (PC) plays a critical role in motor memory consolidation. However, detailed changes in their intrinsic properties during memory consolidation are not well understood. Here, we report alterations in various properties involved in intrinsic excitability, such as the action potential (AP) threshold, AP width, afterhyperpolarization (AHP), and sag voltage, which are associated with the long-term depression of intrinsic excitability following the motor memory consolidation process. We analyzed data recorded from PCs before and 1, 4, and 24 h after cerebellum-dependent motor learning and found that these properties underwent dynamic changes during the consolidation process. We further analyzed data from PC-specific STIM1 knockout (STIM1PKO) mice, which show memory consolidation deficits, and derived intrinsic properties showing distinct change patterns compared with those of wild-type littermates. The levels of memory retention in the STIM1PKO mice were significantly different compared to wild-type mice between 1 and 4 h after training, and AP width, fast- and medium-AHP, and sag voltage showed different change patterns during this period. Our results provide information regarding alterations in intrinsic properties during a particular period that are critical for memory consolidation.
Association between intrarenal venous flow from Doppler ultrasonography and acute kidney injury in patients with sepsis in critical care: a prospective, exploratory observational study
Authors: Fujii Kenichiro , Nakayama Izumi , Izawa Junichi , Iida Noriko , Seo Yoshihiro , Yamamoto Masayoshi , Uenishi Norimichi , Terasawa Teruhiko , Iwata Mitsunaga
Published: July 2023

Background

Intrarenal venous flow (IRVF) patterns assessed using Doppler renal ultrasonography are real-time bedside visualizations of renal vein hemodynamics. Although this technique has the potential to detect renal congestion during sepsis resuscitation, there have been few studies on this method. We aimed to examine the relationship between IRVF patterns, clinical parameters, and outcomes in critically ill adult patients with sepsis. We hypothesized that discontinuous IRVF was associated with elevated central venous pressure (CVP) and subsequent acute kidney injury (AKI) or death.

Methods

We conducted a prospective observational study in two tertiary-care hospitals, enrolling adult patients with sepsis who stayed in the intensive care unit for at least 24 h, had central venous catheters placed, and received invasive mechanical ventilation. Renal ultrasonography was performed at a single time point at the bedside after sepsis resuscitation, and IRVF patterns (discontinuous vs. continuous) were confirmed by a blinded assessor. The primary outcome was CVP obtained at the time of renal ultrasonography. We also repeatedly assessed a composite of Kidney Disease Improving Global Outcomes of Stage 3 AKI or death over the course of a week as a secondary outcome. The association of IRVF patterns with CVP was examined using Student's t-test (primary analysis) and that with composite outcomes was assessed using a generalized estimating equation analysis, to account for intra-individual correlations. A sample size of 32 was set in order to detect a 5-mmHg difference in CVP between IRVF patterns.

Results

Of the 38 patients who met the eligibility criteria, 22 (57.9%) showed discontinuous IRVF patterns that suggested blunted renal venous flow. IRVF patterns were not associated with CVP (discontinuous flow group: mean 9.24 cm H2O [standard deviation: 3.19], continuous flow group: 10.65 cm H2O [standard deviation: 2.53], p = 0.154). By contrast, the composite outcome incidence was significantly higher in the discontinuous IRVF pattern group (odds ratio: 9.67; 95% confidence interval: 2.13–44.03, p = 0.003).

Conclusions

IRVF patterns were not associated with CVP but were associated with subsequent AKI in critically ill adult patients with sepsis. IRVF may be useful for capturing renal congestion at the bedside that is related to clinical patient outcomes.

Graphical abstract
X chromosome inactivation skewing is common in advanced carotid atherosclerotic lesions in females and predicts secondary peripheral artery events
Authors: Buono Michele F. , Benavente Ernest Diez , Daniels Mark , Mol Barend M. , Mekke Joost M. , de Borst Gert J. , de Kleijn Dominique P. V. , van der Laan Sander W. , Pasterkamp Gerard , Onland-Moret Charlotte , Mokry Michal , den Ruijter Hester M.
Published: July 2023

Background and aim

Sex differences in atherosclerosis have been described with female plaques being mostly perceived as stable and fibrous. Sex-specific mechanisms such as mosaic loss of the Y chromosome in men have been linked to cardiovascular health. In women, X-linked mechanisms such as X chromosome inactivation (XCI) skewing is common in several tissues. Yet, information on the role of XCI in female atherosclerotic plaques is lacking. Here, we investigated the presence of XCI skewing in advanced atherosclerotic lesions and its association with cardiovascular risk factors, histological plaque data, and clinical data.

Methods

XCI skewing was quantified in 154 atherosclerotic plaque and 55 blood DNA samples of women included in the Athero-Express study. The skewing status was determined performing the HUMARA assay. Then, we studied the relationship of XCI skewing in female plaque and cardiovascular risk factors using regression models. In addition, we studied if plaque XCI predicted plaque composition, and adverse events during 3-years follow-up using Cox proportional hazard models.

Results

XCI skewing was detected in 76 of 154 (49.4%) plaques and in 27 of 55 (67%) blood samples. None of the clinical risk factors were associated with plaque skewing. Plaque skewing was more often detected in plaques with a plaque hemorrhage (OR [95% CI]: 1.44 [1.06–1.98], P = 0.02). Moreover, skewed plaques were not associated with a higher incidence of composite and major events but were specifically associated with peripheral artery events during a 3-year follow-up period in a multivariate model (HR [95%CI]: 1.46 [1.09–1.97]; P = 0.007).

Conclusions

XCI skewing is common in carotid plaques of females and is predictive for the occurrence of peripheral artery events within 3 years after carotid endarterectomy.
Evidence for sex-specific intramuscular changes associated to physical weakness in adults older than 75 years
Authors: de Jong Jelle C. B. C. , Verschuren Lars , Caspers Martien P. M. , van der Hoek Marjanne D. , van der Leij Feike R. , Kleemann Robert , van den Hoek Anita M. , Nieuwenhuizen Arie G. , Keijer Jaap
Published: July 2023

Background

Physical weakness is a key component of frailty, and is highly prevalent in older adults. While females have a higher prevalence and earlier onset, sex differences in the development of frailty-related physical weakness are hardly studied. Therefore, we investigated the intramuscular changes that differentiate between fit and weak older adults for each sex separately.

Methods

Male (n = 28) and female (n = 26) older adults (75 + years) were grouped on the basis of their ranks according to three frailty-related physical performance criteria. Muscle biopsies taken from vastus lateralis muscle were used for transcriptome and histological examination. Pairwise comparisons were made between the fittest and weakest groups for each sex separately, and potential sex-specific effects were assessed.

Results

Weak females were characterized by a higher expression of inflammatory pathways and infiltration of NOX2-expressing immune cells, concomitant with a higher VCAM1 expression. Weak males were characterized by a smaller diameter of type 2 (fast) myofibers and lower expression of PRKN. In addition, weakness-associated transcriptome changes in the muscle were distinct from aging, suggesting that the pathophysiology of frailty-associated physical weakness does not necessarily depend on aging.

Conclusions

We conclude that physical weakness-associated changes in muscle are sex-specific and recommend that sex differences are taken into account in research on frailty, as these differences may have a large impact on the development of (pharmaceutical) interventions against frailty.

Trial registration number: The FITAAL study was registered in the Dutch Trial Register, with registration code NTR6124 on 14-11-2016 (https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6124 ).

Highlights

• In female, but not male older adults, physical weakness was associated with a higher expression of intramuscular markers for inflammation.

• In male, but not female older adults, physical weakness was associated with a smaller diameter of type 2 (fast) myofibers and lower PRKN expression.

• Fit older adults (of both sexes) maintained expression levels comparable to young participants of weakness related genes, differing from frail participants.
Winery by-products as a feed source with functional properties: dose–response effect of grape pomace, grape seed meal, and grape seed extract on rumen microbial community and their fermentation activity in RUSITEC
Authors: Khiaosa-ard Ratchaneewan , Mahmood Mubarik , Mickdam Elsayed , Pacífico Cátia , Meixner Julia , Traintinger Laura-Sophie
Published: July 2023

Background

Grape and winery by-products have nutritional values for cattle and also contain functional compounds like phenols, which not only bind to protein but can also directly affect microbiota and their function in the rumen. We characterized the nutritional and functional effects of grape seed meal and grape pomace as well as an effective dosage of grape phenols on ruminal microbiota and fermentation characteristics using a rumen simulation technique.

Results

Six diets (each n = 8) were compared including a control diet (CON, no by-product), a positive control diet (EXT, CON + 3.7% grape seed extract on a dry matter (DM) basis), two diets with grape seed meal at 5% (GS-low) and 10% (GS-high), and two diets with grape pomace: at 10% (GP-low) and 20% (GP-high), on a DM basis. The inclusion of the by-product supplied total phenols at 3.4%, 0.7%, 1.4%, 1.3%, and 2.7% of diet DM for EXT, GS-low, GS-high, GP-low, and GP-high, respectively. Diets were tested in four experimental runs. All treatments decreased ammonia concentrations and the disappearances of DM and OM (P < 0.05) compared to CON. EXT and GP-high lowered butyrate and odd- and branch-chain short-chain fatty acids while increased acetate compared to CON (P < 0.05). Treatments did not affect methane formation. EXT decreased the abundance of many bacterial genera including those belonging to the core microbiota. GP-high and EXT consistently decreased Olsenella and Anaerotipes while increased Ruminobacter abundances.

Conclusion

The data suggest that the inclusion of winery by-products or grape seed extract could be an option for reducing excessive ammonia production. Exposure to grape phenols at a high dosage in an extract form can alter the rumen microbial community. This, however, does not necessarily alter the effect of grape phenols on the microbial community function compared to feeding high levels of winery by-products. This suggests the dominant role of dosage over the form or source of the grape phenols in affecting ruminal microbial activity. In conclusion, supplementing grape phenols at about 3% of diet DM is an effective dosage tolerable to ruminal microbiota.
Savoring life during pandemic: an online intervention to promote well-being in emerging adults
Authors: Villani Daniela , Pancini Elisa , Pesce Francesca , Scuzzarella Lucia
Published: July 2023

Background

Savoring, that is the ability to create and increase positive emotions, represents a promising approach to enhance subjective well-being (SWB) in emerging adults. This controlled study aims to investigate the preliminary effects of a self-help e-savoring intervention on increasing savoring beliefs and strategies and SWB in times of the COVID-19 pandemic.

Methods

Forty-nine emerging adult participants were recruited using the snowball sampling method. The experimental group (n = 23) completed six online exercises (two exercises per week for three weeks) while the control group (n = 26) did not receive the intervention. Both groups filled out online questionnaires before and after the intervention. User experience and perceived usefulness of the intervention were assessed for the experimental group.

Results

A repeated measures analysis of variance (ANOVA) revealed a significant increase for the experimental group in savoring beliefs (especially toward the present and the future) and in positive emotions compared to the control group. The perspicuity, attractiveness, and efficiency of the online platform were very positively evaluated, and most participants rated the intervention as useful.

Conclusions

The results of this preliminary study together with the high level of adherence and the appreciation for the intervention indicate the potential of promoting online savoring and positive emotions in emerging adults. Future research could evaluate its long-term effects and verify its results with other age groups.
Simultaneous exercise stress cardiac magnetic resonance and cardiopulmonary exercise testing to elucidate the Fick components of aerobic exercise capacity: a feasibility and reproducibility study and pilot study in hematologic cancer survivors
Authors: Canada Justin M. , McCarty John , Jordan Jennifer H. , Trankle Cory R. , DeCamp Kevin , West Josh D. , Reynolds Mary Ann , Myers Rachel , Sweat Katey , McGhee Virginia , Arena Ross , Abbate Antonio , Hundley W. Gregory
Published: July 2023

Background

Patients treated for hematologic malignancy often experience reduced exercise capacity and increased fatigue; however whether this reduction is related to cardiac dysfunction or impairment of skeletal muscle oxygen extraction during activity is unknown. Cardiopulmonary exercise testing (CPET) coupled with stress cardiac magnetic resonance (ExeCMR), may provide a noninvasive method to identify the abnormalities of cardiac function or skeletal muscle oxygen extraction. This study was performed to determine the feasibility and reproducibility of a ExeCMR + CPET technique to measure the Fick components of peak oxygen consumption (VO2) and pilot its discriminatory potential in hematologic cancer patients experiencing fatigue.

Methods

We studied 16 individuals undergoing ExeCMR to determine exercise cardiac reserve with simultaneous measures of VO2. The arteriovenous oxygen content difference (a-vO2diff) was calculated as the quotient of VO2/cardiac index (CI). Repeatability in measurements of peak VO2, CI, and a-vO2diff was assessed in seven healthy controls. Finally, we measured the Fick determinants of peak VO2 in hematologic cancer survivors with fatigue (n = 6) and compared them to age/gender-matched healthy controls (n = 6).

Results

Study procedures were successfully completed without any adverse events in all subjects (N = 16, 100%). The protocol demonstrated good-excellent test-retest reproducibility for peak VO2 (intraclass correlation coefficient [ICC] = 0.992 [95%CI:0.955–0.999]; P < 0.001), peak CI (ICC = 0.970 [95%CI:0.838–0.995]; P < 0.001), and a-vO2diff (ICC = 0.953 [95%CI:0.744–0.992]; P < 0.001). Hematologic cancer survivors with fatigue demonstrated a significantly lower peak VO2 (17.1 [13.5–23.5] vs. 26.0 [19.7–29.5] mL·kg-1·min-1, P = 0.026) and lower peak CI (5.0 [4.7–6.3] vs. 7.4 [7.0-8.8] L·min-1/m2, P = 0.004) without a significant difference in a-vO2diff (14.4 [11.8–16.9] vs. 13.6 [10.9–15.4] mLO2/dL, P = 0.589).

Conclusions

Noninvasive measurement of peak VO2 Fick determinants is feasible and reliable with an ExeCMR + CPET protocol in those treated for a hematologic malignancy and may offer insight into the mechanisms of exercise intolerance in those experiencing fatigue.
Inequalities at birth: stable socioeconomic differences in birth outcomes in three British cohorts
Authors: Cozzani Marco
Published: July 2023

In this article, I investigate the association between maternal socioeconomic status (SES) and children’s birth outcomes (birth weight) across three different birth cohorts. I also perform mediation analysis to assess the degree to which maternal smoking habits during pregnancy account for this relationship. I draw from three UK cohort studies: the 1958 National Child Developmental Study (NCDS); the 1970 British Cohort (B70); and the 2001 Millennium Cohort study (MCS). There are two main results. First, low-SES mothers are more likely to have children with poor birth outcomes and this association has remained persistent throughout the last 50 years. Second, smoking explains a large part of this association, but only in the two most recent cohorts.
A case of VEXAS syndrome presenting with unusual bone marrow granulomas: a diagnostic dilemma
Authors: Vu Khiem T. , Wolfe Rachel M. , Lambird Jonathan E. , Maracaja Danielle L. V.
Published: July 2023

Background

VEXAS is a recently described inflammatory disease caused by mutations in the UBA1 gene. Symptoms are diverse and include fevers, cartilaginous inflammation, lung inflammation, vasculitis, neutrophilic dermatoses, and macrocytic anemia. Cytoplasmic inclusions in myeloid and erythroid progenitors in the bone marrow are a hallmark feature. Here we report the first case of VEXAS with non-caseating granulomas in the bone marrow.

Case presentation

A 62-year-old Asian male presented with fevers, erythema nodosum, inflammatory arthritis, and periorbital inflammation. Labs were significant for persistently elevated inflammatory markers and macrocytic anemia. Over the years his symptoms and inflammatory markers only improved with glucocorticoids and recurred when prednisone dose was lowered below 15–20 mg daily. He underwent bone marrow biopsy showing non-caseating granulomas and PET scan showing hilar/mediastinal lymphadenopathy. He was initially diagnosed with IgG4-related disease (treated with rituximab) and later sarcoidosis (treated with infliximab). After failing these agents, the possibility of VEXAS was considered and later confirmed by molecular testing.

Conclusions

To the best of our knowledge, this is the first observation of non-caseating granulomas in VEXAS, a cautionary reminder of its non-specificity since misinterpretation can lead to diagnostic delay. VEXAS should be in the differential in patients with symptoms of chronic inflammation responding positively to steroids (but not to B-cell depletion or TNF inhibition), which is in line with previous literature.
Unveiling the enigma: physicians' perceptions of functional neurological disorders in Egypt—a cross-sectional study
Authors: Alamrawy Roa Gamal , Abdel Tawab Alshymaa Mohamed , Omran Hoda Aly Mohamed , Awad Ahmed K. , Rizk Marwa Abdelazim , Abdelrasoul Esraa Ahmed , Etman Amira , Ahmed Dina B. , Ali Essam G. , Ahmed Kamal Manar
Published: July 2023

Background

In medical practice, it is common to see patients who present with physical symptoms for which no disease pathology can be found. The presence of neurological symptoms that are shown to be incompatible with neurological pathophysiology is classically known as “conversion disorder” or “Functional Neurological Symptom Disorder” (FND). While FND is common in Egypt as in the rest of the world, few scientific studies systematically evaluate the degree of knowledge, attitude, and care provided by health care professionals to FND patients. We aimed to assess Egyptian physicians’ perspectives on FND.

Results

A cross-sectional study has been conducted on 152 physicians dealing with FND practicing in Egypt from specialties of psychiatry, neurology, and other specialties. We found that for 45% of the participants, disordered functioning of the nervous system plus psychogenesis was the accepted etiology behind FND. Most participants were significantly not satisfied with their education about FND (p-value 0.01). Psychiatrists and neurologists significantly preferred to use the term “conversion disorder” while other specialties mainly used “psychic” and “Somatization/Somatoform Disorder” (p-value 0.001). Forty-four percent of the participants think they have a good knowledge of functional neurological disorders (FND), while the majority (86.8%) were worried about missing an organic disorder. Psychiatrists were the most confident in diagnosing FND and the most comfortable discussing it with patients (p-values 0.055 and 0.007, respectively).

Conclusion

Here we highlight the common theme of worry about FND patients prevailing among healthcare professionals who are mostly perplexed about the mechanisms behind FND, and how to communicate these symptoms to other professionals and patients themselves. Future directions need to be devoted to minimizing the gap between the research finding and the currently applied care. Better education and teaching about FND may improve patient care.
Polarization-based underwater geolocalization with deep learning
Authors: Bai Xiaoyang , Liang Zuodong , Zhu Zhongmin , Schwing Alexander , Forsyth David , Gruev Viktor
Published: July 2023

Water is an essential component of the Earth’s climate, but monitoring its properties using autonomous underwater sampling robots remains a significant challenge due to lack of underwater geolocalization capabilities. Current methods for underwater geolocalization rely on tethered systems with limited coverage or daytime imagery data in clear waters, leaving much of the underwater environment unexplored. Geolocalization in turbid waters or at night has been considered unfeasible due to absence of identifiable landmarks. In this paper, we present a novel method for underwater geolocalization using deep neural networks trained on $$\sim$$
∼
10 million polarization-sensitive images acquired globally, along with camera position sensor data. Our approach achieves longitudinal accuracy of $$\sim$$
∼
55 km ($$\sim$$
∼
1000 km) during daytime (nighttime) at depths up to $$\sim$$
∼
8 m, regardless of water turbidity. In clear waters, the transfer learning longitudinal accuracy is $$\sim$$
∼
255 km at 50 m depth. By leveraging optical data in conjunction with camera position information, our novel method facilitates underwater geolocalization and offers a valuable tool for untethered underwater navigation.
Negative symptoms in the clinic: we treat what we can describe
Authors: Kirkpatrick Brian , Luther Lauren , Strauss Gregory P.
Published: July 2023

Recent research has led to important changes in the concepts and assessment of negative symptoms in schizophrenia. We review current negative symptom concepts and their clinical implications, as well as new methods of assessing these symptoms. These changes hold promise for improving our understanding and treatment of negative symptoms.
LKB1 signaling is altered in skeletal muscle of a Duchenne muscular dystrophy mouse model
Authors: Boccanegra Brigida , Mantuano Paola , Conte Elena , Cerchiara Alessandro Giovanni , Tulimiero Lisamaura , Quarta Raffaella , Caputo Erika , Sanarica Francesca , Forino Monica , Spadotto Valeria , Cappellari Ornella , Fossati Gianluca , Steinkühler Christian , De Luca Annamaria
Published: July 2023

The potential role of liver kinase B1 (LKB1) in the altered activation of the master metabolic and epigenetic regulator adenosine monophosphate-activated protein kinase (AMPK) in Duchenne muscular dystrophy has not been investigated so far. Hence, we analyzed both gene and protein levels of LKB1 and its related targets in gastrocnemius muscles of adult C57BL/10 mdx mice and D2 mdx mice, a model with a more severe dystrophic phenotype, as well as the sensitivity of the LKB1–AMPK pathway to AMPK activators, such as chronic exercise. Our data show, for the first time, a reduction in the levels of LKB1 and accessory proteins, MO25 and STRADα, in both mdx strains versus the respective wild type, which was further impaired by exercise, in parallel with a lack of further phosphorylation of AMPK. The AMPK-like kinase salt-inducible kinase (SIK) and class II histone deacetylases, along with expression of the HDAC target gene Mef2c, were also altered, supporting an impairment of LKB1-SIK-class II histone deacetylase signaling. Our results demonstrate that LKB1 may be involved in dystrophic progression, paving the way for future preclinical studies.
Common and uncommon lesions of the vulva and vagina on magnetic resonance imaging: correlations with pathological findings
Authors: Ning Yan , Ling Rennan , Zhang Feiran , Zhang Guofu , Zhang He
Published: July 2023

Vulvar and vaginal lesions representing a wide spectrum of diseases in female lower genital tract diseases make up a small part of all gynecological etiologies. Many of them are rare etiologies and are reported in case-reports studies. Translabial and transperineal ultrasound are modalities of choice for the first evaluation of perineal lesions. MRI is usually performed to determine the etiology of the lesions and stage. Benign lesions of the vulva and vagina usually manifest as simple cystic (vestibular cyst or endometrioma) or solid lesions (leiomyoma or angiofibroblastoma), while malignancies usually appear as large, solid masses and fill into both vaginal and perineal area. Post-contrast images play an important role in establishing a differential diagnosis, however, some benign lesions can also exhibit a vivid enhancement. Knowledge about radiologic-associated pathological manifestations may aid clinicians in better understanding these pathologies, especially for some rare lesions, and making a proper diagnosis before invasive procedures.
Human examination and artificial intelligence in cephalometric landmark detection—is AI ready to take over?
Authors: Indermun Suvarna , Shaik Shoayeb , Nyirenda Clement , Johannes Keith , Mulder Riaan
Published: July 2023

Objectives:

To compare the precision of two cephalometric landmark identification methods, namely a computer-assisted human examination software and an artificial intelligence program, based on South African data.

Methods:

This retrospective quantitative cross-sectional analytical study utilized a data set consisting of 409 cephalograms obtained from a South African population. 19 landmarks were identified in each of the 409 cephalograms by the primary researcher using the two programs [(409 cephalograms x 19 landmarks) x 2 methods = 15,542 landmarks)]. Each landmark generated two coordinate values (x, y), making a total of 31,084 landmarks. Euclidean distances between corresponding pairs of observations was calculated. Precision was determined by using the standard deviation and standard error of the mean.

Results:

The primary researcher acted as the gold-standard and was calibrated prior to data collection. The inter- and intrareliability tests yielded acceptable results. Variations were present in several landmarks between the two approaches; however, they were statistically insignificant. The computer-assisted examination software was very sensitive to several variables. Several incidental findings were also discovered. Attempts were made to draw valid comparisons and conclusions.

Conclusions:

There was no significant difference between the two programs regarding the precision of landmark detection. The present study provides a basis to: (1) support the use of automatic landmark detection to be within the range of computer-assisted examination software and (2) determine the learning data required to develop AI systems within an African context.
Age estimation based on 3D pulp segmentation of first molars from CBCT images using U-Net
Authors: Song Yangjing , Yang Huifang , Ge Zhipu , Du Han , Li Gang
Published: July 2023

Objective:

To train a U-Net model to segment the intact pulp cavity of first molars and establish a reliable mathematical model for age estimation.

Methods:

We trained a U-Net model by 20 sets of cone-beam CT images and this model was able to segment the intact pulp cavity of first molars. Utilizing this model, 239 maxillary first molars and 234 mandibular first molars from 142 males and 135 females aged 15–69 years old were segmented and the intact pulp cavity volumes were calculated, followed by logarithmic regression analysis to establish the mathematical model with age as the dependent variable and pulp cavity volume as the independent variable. Another 256 first molars were collected to estimate ages with the established model. Mean absolute error and root mean square error between the actual and the estimated ages were used to assess the precision and accuracy of the model.

Results:

The dice similarity coefficient of the U-Net model was 95.6%. The established age estimation model was Age=148.671-30.262×ln⁡V (V is the intact pulp cavity volume of the first molars). The coefficient of determination (R2), mean absolute error and root mean square error were 0.662, 6.72 years, and 8.26 years, respectively.

Conclusion:

The trained U-Net model can accurately segment pulp cavity of the first molars from three-dimensional cone-beam CT images. The segmented pulp cavity volumes could be used to estimate the human ages with reasonable precision and accuracy.
Prediction of self-efficacy in recognizing deepfakes based on personality traits
Authors: Abraham Juneman , Putra Heru Alamsyah , Prayoga Tommy , Warnars Harco Leslie Hendric Spits , Manurung Rudi Hartono , Nainggolan Togiaratua
Published: July 2023

Background: While deepfake technology is still relatively new, concerns are increasing as they are getting harder to spot. The first question we need to ask is how good humans are at recognizing deepfakes - realistic-looking videos or images that show people doing or saying things that they never actually did or said generated by an artificial intelligence-based technology. Research has shown that an individual’s self-reported efficacy correlates with their ability to detect deepfakes. Previous studies suggest that one of the most fundamental predictors of self-efficacy are personality traits. In this study, we ask the question: how can people’s personality traits influence their efficacy in recognizing deepfakes?  Methods: Predictive correlational design with a multiple linear regression data analysis technique was used in this study. The participants of this study were 200 Indonesian young adults. Results: The results showed that only traits of Honesty-humility and Agreeableness were able to predict the efficacy, in the negative and positive directions, respectively. Meanwhile, traits of Emotionality, Extraversion, Conscientiousness, and Openness cannot predict it. Conclusion: Self-efficacy in spotting deepfakes can be predicted by certain personality traits.
Weekly paclitaxel, carboplatin and cetuximab (PCC) combination followed by nivolumab in platinum-sensitive recurrent and /or metastatic squamous cell carcinoma of head and neck: a retrospective analysis from two institutions in India
Authors: Chandrakanth M V , Agarwala Vivek , Mondal Pradip , Chanana Raajit , Parthasarathy K M , Dutta Sourav , Dhar Harsh , Mallick Suman , Das Sayan , Banerjee Devmalya , Faizan Md Arif , Basu Moinak , Kumar Subhabrata
Published: July 2023

Background: First line (1L) TP-Ex-like regimen followed by 2nd-line (2L) immunotherapy represents one of the standards of care in platinum-sensitive recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN). We report our experience from 2 tertiary care institutions of India. 

Methods: This is a retrospective analysis of consecutive patients of platinum-sensitive R/M SCCHN treated with 1L weekly paclitaxel, carboplatin, and cetuximab (PCC) regimen followed by cetuximab maintenance (if non-progressive) or 2L nivolumab or oral metronomic chemotherapy (OMCT) on progression. Overall response rates (ORR), progression-free survival after 1L and 2L (PFS-1 & PFS-2), overall survival (OS), and safety were evaluated. 

Results: The study included 54 patients; median age 56.5 years; 89% men; 11% had cardiac dysfunction; 13% had renal dysfunction. After 1L PCC, ORR was 59.3%; median PFS-1 was 7.031 months; 61% had progression; 35% were treated with nivolumab and 18% with OMCT. The ORR was 26.3% (nivolumab) and 10% (OMCT). Median PFS-2 was 6.5 months (nivolumab) and 2 months (OMCT). The median OS was 15.01 months (entire cohort), 20.6 months (nivolumab), and 7 months (OMCT). Grade III/IV adverse events on PCC included neutropenia (31.4%), anaemia (35.1%), thrombocytopenia (7.4%), febrile neutropenia (11.1%), and skin reaction (16.6%); no Grade-III/IV treatment-related toxicities on 2L. 

Conclusions: 1L weekly PCC is an effective regimen for palliative therapy of platinum- sensitive R/MSCCHN with an acceptable toxicity profile. The addition of 2L nivolumab on progression further improves the outcomes.
Re-starting anticoagulation and antiplatelets after gastrointestinal bleeding: A systematic review
Authors: Slouha Ethan , Jensen Haley , Fozo Hope , Raj Rhea , Thomas Sneha , Gorantla Vasavi
Published: July 2023

Background: Gastrointestinal bleeds (GIB) are associated with high morbidity and mortality, with upper GIB accounting for 20,000 deaths annually in the United States of America. Accurate risk stratification is essential in determining and differentiating high-risk versus low-risk patients, as low-risk patients have an overall better prognosis. Patients taking antithrombotics to reduce the risk of thromboembolic events have a 4% chance of developing a GIB. This then places physicians in a difficult position as they must perform a risk-and-benefit analysis of whether to reinstate antithrombotics after a major GIB. This systematic review aims to assess the general trends in time for resuming anticoagulation in the setting of upper GI bleed.

Methods: A literary search of three different databases was performed by three independent reviewers. The research databases included PubMed, ScienceDirect, and ProQuest. Specific keywords were used to narrow the search and articles were screened based on inclusion and exclusion criteria.

Results: Our initial search generated 11,769 potential articles and 22 articles were ultimately used for this review using specific inclusion and exclusion criteria. There is an increase in thrombotic events following a GIB if anticoagulants are not resumed. We also found that the best time to resume therapy was 15-30 days post-GIB.

Conclusions: Therefore, the decision to resume anticoagulation therapy should consider the patients’ medical history and should fall within 15-30 days post-GIB.
Case Report: An in-depth look into apocrine carcinoma of the axilla - a rare case presentation.
Authors: Naseri Dr. Suhit , Shukla Dr. Samarth , Acharya Dr. Sourya , Vagha Dr. Sunita
Published: July 2023

Apocrine carcinoma is an extremely rare malignant cutaneous neoplasm that usually arises in areas with a high density of apocrine glands.1 Diagnosis can be challenging as tumours share histological and immunophenotypic characteristics with them. At first evaluation, the disease is often assumed to be benign. There have been approximately 100 reports of apocrine neoplasms in the literature.

A 48-year-old male presented with a right axillary mass which increased in size over a period of 2 years. The patient was reported to have had ayurvedic therapy, but his swelling remained unchanged. Axillary lymph nodes were palpable. USG axilla suggested a well-defined fungating solid isoechoic lesion. USG neck did not reveal any abnormality. The mass was surgically excised as a whole by removing the overlying skin with margins and lymph node excision. The patient was diagnosed with primary apocrine carcinoma after surgical excision. The differentials include adenocarcinoma of breast and prostate and apocrine adenoma. There are no established standards for the care of this form of carcinoma due to its rarity and the absence of clinical studies. A literature evaluation and further reporting will aid in developing diagnostic standards and the most efficient treatment options.