bluuebunny/crossref_metadata_2025 huggingface dataset:
A noise-controlling method by hybrid current-stimulation and voltage-measurement for electrical impedance tomography (HCSVM-EIT)
Authors: Gao Zengfeng , Darma Panji Nursetia , Sun Bo , Kawashima Daisuke , Takei Masahiro
Published: September 2023

Image reconstruction in electrical impedance tomography (EIT) is a typical ill-posed inverse problem, from which the stability of conductivity reconstruction affects the reliability of physiological parameters evaluation. In order to improve the stability, the effect of boundary voltage noise on conductivity reconstruction should be controlled. A noise-controlling method based on hybrid current-stimulation and voltage-measurement for EIT (HCSVM-EIT) is proposed for stable conductivity reconstruction. In HCSVM-EIT, the boundary voltage is measured by one current-stimulation and voltage-measurement pattern (high-SNR pattern) with a higher signal-to-noise ratio (SNR); the sensitivity matrix is calculated by another current-stimulation and voltage-measurement pattern (low-cond pattern) with a lower condition number; the boundary voltage is then transformed from the high-SNR pattern into the low-cond pattern by multiplying by an optimized transformation matrix for image reconstruction. The stability of conductivity reconstruction is improved by combining the advantages of the high-SNR pattern for boundary voltage measurement and the low-cond pattern for sensitivity matrix calculation. The simulation results show that the HCSVM-EIT increases the correlation coefficient (CC) of conductivity reconstruction. The experiment results show that the CC of conductivity reconstruction of the human lower limb is increased from 0.3424 to 0.5580 by 62.97% compared to the quasi-adjacent pattern, and from 0.4942 to 0.5580 by 12.91% compared to the adjacent pattern. In conclusion, the stable conductivity reconstruction with higher CC in HCSVM-EIT improves the reliability of physiological parameters evaluation for disease detection.
Effects of freeze-thaw cycles on the size distribution and stability of soil aggregate in the permafrost regions of the Qinghai-Tibetan Plateau
Authors: Dong Chenjie , Gu Yuzheng , Jia Yinglan , Wei Peijie , Jin Jingwei , Deng Yanfang , Yang Peizhi , Chen Shengyun
Published: September 2023

As the basic units of soil structure, soil aggregate is essential for maintaining soil stability. Intensified freeze–thaw cycles have deeply affected the size distribution and stability of aggregate under global warming. To date, it is still lacking about the effects of freeze–thaw cycles on aggregate in the permafrost regions of the Qinghai-Tibetan Plateau (QTP). Therefore, we investigated the effects of diurnal and seasonal freeze–thaw processes on soil aggregate. Our results showed that the durations of thawing and freezing periods in the 0–10 cm layer were longer than in the 10–20 cm layer, while the opposite results were observed during completely thawed and frozen periods. Freeze–thaw strength was greater in the 0–10 cm layer than that in the 10–20 cm layer. The diurnal freeze–thaw cycles have no significant effect on the size distribution and stability of aggregate. However, < 0.25 mm fraction dominated wet sieving aggregate with the highest proportion during thawing period, while the < 1 mm fraction reached the highest during completely frozen period in the 10–20 cm layer (P < 0.05). Likewise, the mean weight diameter and water-stable aggregate were decreased during thawing period compared with the other periods, which were influenced by soil microbial biomass carbon and belowground biomass. Hence, the seasonal freeze–thaw processes destroyed macro-aggregate (> 0.25 mm) and reduced aggregate stability. Our study has scientific guidance for evaluating the effects of freeze–thaw cycles on soil steucture and provides a theoretical basis for further exploration on soil and water conservation in the permafrost regions of the QTP.
Influence of neutron and gamma irradiation on the electrocaloric properties of Mn-doped 0.9Pb(Mg1/3Nb2/3)O3–0.1PbTiO3 ceramics
Authors: Sarkar Ankita , Šadl Matej , Jazbec Anže , Snoj Luka , Drnovšek Silvo , Rojac Tadej , Brennecka Geoff L , Uršič Hana , Malič Barbara
Published: September 2023

The influence of neutron and gamma irradiation on the low- and high-field dielectric and electrocaloric (EC) properties of Mn-doped 0.9Pb(Mg1/3Nb2/3)O3–0.1PbTiO3 (PMN–10PT) ceramic is studied. Upon exposure to neutron fluences of up to 1017 cm−2 and gamma-ray doses of up to 1200 kGy the Mn-doped PMN–10PT exhibits a lower saturated polarization, increased internal bias field and reduced EC temperature change. In comparison, the respective properties of the undoped PMN–10PT remain almost unchanged upon exposure to neutrons and gamma rays. In Mn-doped PMN–10PT, the acceptor-oxygen vacancy defect complexes, introduced via doping, contribute to the lowering of the threshold radiation dose that the material survives without noticeable changes in properties. Radiation-induced degradation of the EC response of Mn-doped PMN–10PT can be partially healed by annealing at 450 °C. The study provides guidance for designing EC ceramic materials for solid-state cooling applications in environments of high ionizing radiation, such as the medical field or space technologies.
Development of compact voltage level-up shifter for nano-second delay system-on-chip applications
Authors: Sudhakar M Venkata , Gutta Uma Sankar
Published: September 2023

The Level Shifter is made with two inverters and a Wilson current mirror to use less energy. In order to reduce the amount of leaking power, this study suggests using a combination of super-cut-off draw-down and stacked pull-up networks. The design also incorporates multi-threshold complementary-metal-oxide-semiconductor (MTCMOS) technology, which, consists of sleeper transistors that are able to boosts performance without increasing either power usage or size. The designed device can be used to shift voltage in between 0.4 V and 1.2 V. To suit nano-scale uses, the circuit’s operating range and performance factors (such as power, latency, and area) were fine-tuned. According to the results, ‘level-up’ transitions typically consume 148.6nW of active power and have an average delay of 1.19 ns at 1 MHz transmission rates. The post-layout model indicated that the recommended plan would need 9.47 μm2 of floor space. The results are analyzed in Cadence Virtuoso using 45 nm techniques.
A fully interpretable machine learning model for increasing the effectiveness of urine screening
Authors: Del Ben Fabio , Da Col Giacomo , Cobârzan Doriana , Turetta Matteo , Rubin Daniela , Buttazzi Patrizio , Antico Antonio
Published: September 2023

Objectives

This article addresses the need for effective screening methods to identify negative urine samples before urine culture, reducing the workload, cost, and release time of results in the microbiology laboratory. We try to overcome the limitations of current solutions, which are either too simple, limiting effectiveness (1 or 2 parameters), or too complex, limiting interpretation, trust, and real-world implementation (“black box” machine learning models).

Methods

The study analyzed 15,312 samples from 10,534 patients with clinical features and the Sysmex Uf-1000i automated analyzer data. Decision tree (DT) models with or without lookahead strategy were used, as they offer a transparent set of logical rules that can be easily understood by medical professionals and implemented into automated analyzers.

Results

The best model achieved a sensitivity of 94.5% and classified negative samples based on age, bacteria, mucus, and 2 scattering parameters. The model reduced the workload by an additional 16% compared to the current procedure in the laboratory, with an estimated financial impact of €40,000/y considering 15,000 samples/y. Identified logical rules have a scientific rationale matched to existing knowledge in the literature.

Conclusions

Overall, this study provides an effective and interpretable screening method for urine culture in microbiology laboratories, using data from the Sysmex UF-1000i automated analyzer. Unlike other machine learning models, our model is interpretable, generating trust and enabling real-world implementation.
Assessment of a large language model’s utility in helping pathology professionals answer general knowledge pathology questions
Authors: Benirschke Robert C , Wodskow Joshua , Prasai Kritika , Freeman Andrew , Lee John M , Groth John
Published: September 2023

Objectives

To assess the utility and performance of the large language model ChatGPT 4.0 regarding accuracy, completeness, and its potential as a time-saving tool for pathologists and laboratory directors.

Methods

A deidentified database of questions previously sent to pathology residents from health care providers was used as a source of general knowledge–type pathology questions. These questions were submitted to the large language model and the responses graded by subject matter experts in different pathology subspecialties. The grading criteria assessed accuracy, completeness, and the potential time savings for helping the pathologist craft the response.

Results

Overall, respondents thought that most of the answers would take less than 5 minutes of additional work to be used (85%). Accuracy and completeness for the 61 questions was high, with 98% of responses being at least “completely or mostly accurate” and 82% of responses “containing all relevant information.” Of the respondents, 97% stated that the response would have “zero or near-zero potential for medical harm,” and all thought the tool had potential to save time in constructing answers to health care providers’ queries. Performance was similar in both Anatomic Pathology (AP) and Clinical Pathology (CP), with the only exception being some relevant information was excluded in 46% of AP answers vs only 10% in CP (P < .01).

Conclusions

ChatGPT version 4.0 gave responses that were predominantly accurate and complete for general knowledge–type pathology questions. With further research and when reviewed by a pathologist or laboratorian, this could facilitate its use as a pathologist’s aid in answering questions from health care providers.
Superior detection rate of plasma cell FISH using FACS-FISH
Authors: Gagnon Marie-France , Midthun Sally M , Fangel James A , Schuh Cynthia M , Luoma Ivy M , Pearce Kathryn E , Meyer Reid G , Ailawadhi Sikander , Arribas Mariano J , Braggio Esteban , Fonseca Rafael , Rajkumar S Vincent , Zepeda-Mendoza Cinthya , Xu Xinjie , Greipp Patricia T , Timm Michael M , Otteson Gregory E , Shi Min , Jevremovic Dragan , Olteanu Horatiu , Peterson Jess F , Ketterling Rhett P , Kumar Shaji , Baughn Linda B
Published: September 2023

Objectives

Fluorescence in situ hybridization (FISH) for plasma cell neoplasms (PCNs) requires plasma cell (PC) identification or purification strategies to optimize results. We compared the efficacy of cytoplasmic immunoglobulin FISH (cIg-FISH) and fluorescence-activated cell sorting FISH (FACS-FISH) in a clinical laboratory setting.

Methods

The FISH analysis results of 14,855 samples from individuals with a suspected PCN subjected to cytogenetic evaluation between 2019 and 2022 with cIg-FISH (n = 6917) or FACS-FISH (n = 7938) testing were analyzed.

Results

Fluorescence-activated cell sorting–FISH increased the detection rate of abnormalities in comparison with cIg-FISH, with abnormal results documented in 54% vs 50% of cases, respectively (P < .001). It improved the detection of IGH::CCND1 (P < .001), IGH::MAF (P < .001), IGH::MAFB (P < .001), other IGH rearrangements (P < .001), and gains/amplifications of 1q (P < .001), whereas the detection rates of IGH::FGFR3 fusions (P = .3), loss of 17p (P = .3), and other abnormalities, including hyperdiploidy (P = .5), were similar. Insufficient PC yield for FISH analysis was decreased between cIg-FISH and FACS-FISH (22% and 3% respectively, P < .001). Flow cytometry allowed establishment of ploidy status in 91% of cases. In addition, FACS-FISH decreased analysis times, workload efforts, and operating costs.

Conclusions

Fluorescence-activated cell sorting–FISH is an efficient PC purification strategy that affords significant improvement in diagnostic yield and decreases workflow requirements in comparison with cIg-FISH.
Implementation of a pharmacy-driven rapid bacteremia response program
Authors: Wilde Ashley M , Song Matthew , Allen W Paul , Junkins Alan D , Frazier James M , Moore Sarah E , Schulz Paul S
Published: September 2023

Purpose

This report describes a comprehensive pharmacy-driven rapid bacteremia response program.

This novel program positioned the pharmacy department at a large, community health system to receive and respond to critical microbiologic diagnostic testing results, 24/7/365. The program empowered pharmacists to provide centralized, comprehensive care including assessing blood culture Gram stain results, adjusting antibiotic therapy per protocol, ordering repeat blood cultures, analyzing and interpreting rapid molecular diagnostic test results, placing orders for contact isolation, and communicating antibiotic recommendations to the treatment team. In the first year after program implementation, 2,282 blood culture Gram stains and 2,046 rapid diagnostic test results were called in to the pharmacy department. The program reduced the median time to effective therapy in patients who did not already have active antimicrobial orders from over 10 hours to less than 1 hour. Based on the Gram stain results, antibiotics were started per protocol in 34.2% of patients. Based on the rapid molecular diagnostic test results, adjustments were made to antibiotic regimens in 55.7% of cases after discussion with a provider. Of these adjustments, 39.9% were for escalation of antibiotics and 37.7% were for de-escalation of antibiotics.

Conclusion

By expanding the scope of pharmacy practice, barriers to optimizing clinical care were overcome.
Hoist by the Colonizer’s Own Device? Law Reporting in Mandatory Palestine
Authors: Sagy Yair , Katvan Eyal
Published: September 2023

This article tells the history of the Palestine Law Reports series (PLR), introduced in 1934 to Mandate-ruled Palestine. It unearths discussions that preceded the PLR’s publications following a campaign for authorized law reporting launched by lawyers in Palestine in the 1920s to 1930s. Canvassing a broad institutional context for the emergence of the PLR, we argue that in launching the campaign local lawyers sought not only to render Palestinian common law more predictable and amenable to professional handling, but also to approximate the role granted in the metropole and the common law tradition to practicing lawyers in propagating binding precedents. Local lawyers wanted to have a slice of the action of creating a local common law and in designing the Palestinian legal landscape. Unsurprisingly, they were met with the opposition of Chief Justice McDonnell, who sought to control the PLR enterprise, resisting non-judicial involvement in its editing and production. Finally, the article argues that, regardless of McDonnell’s motivations, from an institutional point of view, his achievement in laying down a foundational institution for the generation of a local common law is momentous. He therefore emerges from our analysis as one of the chief architects of the common law in Palestine, and—to this day—in Israel.
Sequential diversification with Miocene extinction and Pliocene speciation linked to mountain uplift explains the diversity of the African rain forest clade Monodoreae (Annonaceae)
Authors: Dagallier Léo-Paul M J , Condamine Fabien L , Couvreur Thomas L P
Published: September 2023

Background and Aims

Throughout the Cenozoic, Africa underwent several climatic and geological changes impacting the evolution of tropical rain forests (TRFs). African TRFs are thought to have extended from east to west in a ‘pan-African’ TRF, followed by several events of fragmentation during drier climate periods. During the Miocene, climate cooling and mountain uplift led to the aridification of tropical Africa and open habitats expanded at the expense of TRFs, which probably experienced local extinctions. However, in plants, these drivers were previously inferred using limited taxonomic and molecular data. Here, we tested the impact of climate and geological changes on diversification within the diverse clade Monodoreae (Annonaceae) composed of 90 tree species restricted to African TRFs.

Methods

We reconstructed a near-complete phylogenetic tree, based on 32 nuclear genes, and dated using relaxed clocks and fossil calibrations in a Bayesian framework. We inferred the biogeographical history and the diversification dynamics of the clade using multiple birth–death models.

Key Results

Monodoreae originated in East African TRFs ~25 million years ago (Ma) and expanded toward Central Africa during the Miocene. We inferred range contractions during the middle Miocene and document important connections between East and West African TRFs after 15–13 Ma. Our results indicated a sudden extinction event during the late Miocene, followed by an increase in speciation rates. Birth–death models suggested that African elevation change (orogeny) is positively linked to speciation in this clade.

Conclusion

East Africa is inferred as an important source of Monodoreae species, and possibly for African plant diversity in general. Our results support a ‘sequential scenario of diversification’ in which increased aridification triggered extinction of TRF species in Monodoreae. This was quickly followed by fragmentation of rain forests, subsequently enhancing lagged speciation resulting from vicariance and improved climate conditions. In contrast to previous ideas, the uplift of East Africa is shown to have played a positive role in Monodoreae diversification.
Low levels of mouse sperm chromatin fragmentation delay embryo development
Authors: Nguyen Hieu , Ribas-Maynou Jordi , Wu Hongwen , Quon Beverly , Inouye Tracy , Walker Brienne , Langaman Caitlin , Huang Thomas T F , Ward W Steven
Published: September 2023

We previously demonstrated that MnCl2 induces double-stranded DNA breaks in sperm in a process that we term as sperm chromatin fragmentation. Here, we tested if the levels of double-stranded DNA breaks were corelated to the concentration of MnCl2, and we compared this to another agent that causes single-stranded DNA breaks, H2O2. We found that both methods have the advantage of inducing DNA breaks in a concentration-dependent manner. Mouse sperm were treated with varying concentrations of either H2O2 or MnCl2, and the DNA damage was assessed by pulse-field gel electrophoresis, and the alkaline and neutral comet assays. Oocytes were injected with either treated sperm and the resulting embryos analyzed with an embryoscope to detect subtle changes in embryonic development. We confirmed that H2O2 treatment induced primarily single-stranded DNA breaks and MnCl2 induced primarily double-stranded DNA breaks, indicating different mechanisms of damage. These sperm were injected into oocytes, and the development of the resulting embryos followed with an embryoscope equipped with time lapse recording. We found that aberrations in early embryonic development by day 2 with even the lowest levels of DNA damage and that the levels of embryonic aberrations correlated to the concentration of either H2O2 or MnCl2. Low levels of H2O2 caused significantly more aberrations in embryonic development than low levels of MnCl2 even though the levels of DNA damage as measured by comet assays were similar. These data demonstrate that even low levels of sperm DNA damage cause delays and arrests in embryonic development.
Spexin role in human granulosa cells physiology and PCOS: expression and negative impact on steroidogenesis and proliferation
Authors: Kurowska Patrycja , Dawid Monika , Oprocha Julia , Respekta Natalia , Serra Loïse , Estienne Anthony , Pawlicki Piotr , Kotula-Balak Małgorzata , Guérif Fabrice , Dupont Joelle , Rak Agnieszka
Published: September 2023

Spexin (SPX) is a novel neuropeptide and adipokine negatively correlated with obesity and insulin resistance. A recent study investigated expression and regulatory function of SPX in the hypothalamus and pituitary; however, the effect on ovarian function is still unknown. The aim of this study was to characterize the expression of SPX and its receptors, galanin receptors 2 and 3 (GALR2/3), in the human ovary and to study its in vitro effect on granulosa cells (GC) function. Follicular fluid (FF) and GC were obtained from normal weight and obese healthy and diagnosed with polycystic ovarian syndrome (PCOS) women. Expression of SPX and GALR2/3 in the ovary was studied by qPCR, western blot, and immunohistochemistry. The level of SPX in FF was assessed by enzyme-linked immunosorbent assay. The in vitro effect of recombinant human SPX on GC proliferation, steroidogenesis, and signaling pathways (MAP3/1, STAT3, AKT, PKA) was analyzed. Moreover, GC proliferation and estradiol (E2) secretion were measured with and without an siRNA against GALR2/3 and pharmacological inhibition of the above kinases. The results showed that both the SPX concentration in FF and its gene expression were decreased in GC of obese and PCOS women, while the protein expression of GALR2/3 was increased. We noted that SPX reduced GC proliferation and steroidogenesis; these effects were mediated by GALR2/3 and kinases MAP3/1, AKT, and STAT3 for proliferation or kinases MAP3/1 and PKA for E2 secretion. The obtained data clearly documented that SPX is a novel regulator of human ovarian physiology and possibly plays a role in PCOS pathogenesis.
The role of enhancers in psoriasis and atopic dermatitis
Authors: Sui Jennifer Y , Eichenfield Dawn Z , Sun Bryan K
Published: September 2023

Regulatory elements, particularly enhancers, play a crucial role in disease susceptibility and progression. Enhancers are DNA sequences that activate gene expression and can be affected by epigenetic modifications, interactions with transcription factors (TFs) or changes to the enhancer DNA sequence itself. Altered enhancer activity impacts gene expression and contributes to disease. In this review, we define enhancers and the experimental techniques used to identify and characterize them. We also discuss recent studies that examine how enhancers contribute to atopic dermatitis (AD) and psoriasis. Articles in the PubMed database were identified (from 1 January 2010 to 28 February 2023) that were relevant to enhancer variants, enhancer-associated TFs and enhancer histone modifications in psoriasis or AD. Most enhancers associated with these conditions regulate genes affecting epidermal homeostasis or immune function. These discoveries present potential therapeutic targets to complement existing treatment options for AD and psoriasis.
Facioscapulohumeral muscular dystrophy’s game of homeodomains: therapy wants a biomarker as a sword wants a whetstone
Authors: Kyba Michael , Bosnakovski Darko
Published: September 2023

This scientific commentary refers to ‘The FSHD muscle-blood biomarker: a circulating transcriptomic biomarker for clinical severity in facioscapulohumeral muscular dystrophy’, by Banerji et al. (https://doi.org/10.1093/braincomms/fcad221).
Variation in the practice of wide local excision for melanoma in Ireland and the UK: a questionnaire survey
Authors: O’Connor Eileen , O’Connor Cathal , O’Connell Garret , Peach Howard , O’Shea Sally
Published: September 2023

Background

Wide local excision (WLE) is standard practice in the management of melanoma, but no national or international guidelines exist regarding its technique.

Objectives

To assess variation in the practice of WLE and to explore the effect of clinicians’ specialty and grade on such variation.

Methods

This was an international, anonymized, cross-sectional study. An online questionnaire was distributed to the Irish Association of Dermatologists, British Association of Dermatologists, British Association of Plastic and Reconstructive and Aesthetic Surgeons, Melanoma Focus and BioGenoMEL members.

Results

Of 128 respondents, 57% were dermatologists and 38% plastic surgeons. Most (80%) were consultants. Almost all clinicians learned their technique from colleagues (99%) ‘on the job’, although 21% also used textbooks or other media as part of WLE training. There was significant variation in planning and performing WLE: 59% considered margins already achieved, 71% marked margins with the skin relaxed. For 1 cm WLE, 84% delineated 1 cm from the edge of the scar; with a greater proportion of plastic surgeons than dermatologists marking from the centre of the scar (P < 0.05). Most followed a longitudinal/oblique axis on the limbs for WLE (81%). Only 40% sent ‘dog ears’ for histology. Most (70%) incised through the marked line, 27% incised outside it. Most (79%) excised to deep fascia, 18% to the next biological margin.

Conclusions

This study demonstrates significant variation among clinicians performing WLE, an essential component of melanoma management. We postulate that this could have an impact on patient outcomes. A consensus statement should be developed, to achieve more consistency in the practice of WLE.
Cardiac sarcoidosis preceded by sick sinus syndrome presenting as biventricular involvement and intracardiac giant thrombus: a case report
Authors: Hirai Akeo , Shiraishi Yasuyuki , Fukuda Keiichi , Fujita Jun
Published: September 2023

Background

Sarcoidosis is a granulomatous disorder characterized by the formation of non-necrotizing granulomas in various organs. Cardiac sarcoidosis presents with various clinical, anatomical, and electrophysiological manifestations. As cardiac involvement is related to adverse outcomes, the early diagnosis of cardiac sarcoidosis is crucial and sometimes challenging.

Case summary

A 65-year-old woman was initially treated for sick sinus syndrome (SSS) with normal cardiac function. Cardiac conduction defects and biventricular dysfunction continued to progress over a short clinical course, and the patient was eventually referred to our hospital for further investigation and treatment of cardiogenic shock due to pacemaker pacing failure. An echocardiography revealed a large thrombus formation in the right ventricle and atrium. An urgent thrombectomy was performed, and myocardial biopsy confirmed the diagnosis of cardiac sarcoidosis. Steroid pulse therapy was initiated and was effective in treating the cardiogenic shock. One year after discharge, the patient manifested with sustained ventricular tachycardia and ultimately died of severe cardiac pump failure. On autopsy, diffuse fibrotic tissues were noted in both ventricles and atria.

Discussion

While conduction abnormalities, such as right bundle brunch block and atrioventricular block, are common clinical manifestations, SSS is rarely reported as a primary manifestation of cardiac sarcoidosis. Thus, clinicians should ensure that sufficient investigations are carried out when diagnosing idiopathic SSS.
Prominent myocardial bridging as a first clue to recognize haemorrhagic shock during percutaneous coronary intervention: a case report
Authors: Aono Mio , Miyoshi Toru , Higaki Akinori , Yamaguchi Osamu
Published: September 2023

Background

Haemorrhage at the puncture site is a serious complication of percutaneous coronary intervention (PCI).

Case summary

A 73-year-old man underwent transfemoral intervention because of stable angina pectoris. After a rotational atherectomy, an everolimus-eluting stent was implanted from the left main trunk to the proximal site of the left anterior descending (LAD) artery. We also recognized that myocardial bridging was significantly induced at the middle portion of the LAD, which was not evident before the PCI. We suspected puncture-related haemorrhage and immediately performed lower limb arteriography. As a result, contrast media extravasation was observed at the branch of the right inferior epigastric artery. Finally, we performed coil embolization into the left common femoral artery, and the extravasation successfully disappeared. Four months later, he underwent coronary angiography. There were no findings of myocardial bridging.

Discussion

Myocardial bridging during a PCI procedure may indicate hypercontraction because of haemorrhage.
Late-onset MELAS syndrome in a 46-year-old man with initial symptom of chest tightness: a case report
Authors: Wang Ai , Zhao Ji , Zhao Yun , Yan Yan
Published: September 2023

Background

Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder caused by mutations in mitochondrial DNA, resulting in impaired energy production and affecting multiple organs. We present a suspected MELAS syndrome case with the initial symptom of chest tightness.

Case summary

A 46-year-old man sought medical attention due to progressively worsening chest tightness during physical activity. He had been receiving treatment for type 2 diabetes for 15 years. One year ago, he presented with symptoms of hearing impairment. Transthoracic echocardiography revealed increased thickness of the left ventricular wall. Serum protein electrophoresis showed no evidence of light-chain amyloidosis, and the 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scan showed no definite uptake in the heart muscle. The patient’s head magnetic resonance imaging (MRI) indicated lacunar infarcts. The lactate threshold test was positive. The biopsy of the skeletal muscle showed broken red fibre infiltration on modified Gomori trichrome staining, and electron microscopy revealed signs of mitochondrial cardiomyopathy, including mild mitochondrial swelling, lipid accumulation, and myofibril damage. A whole-exome genetic test was used to detect the m.3243A>G mutation in the MT-TL1 gene. Based on these findings, MELAS syndrome was the most probable diagnosis.

Discussion

The patient presented with chest tightness in adulthood, without any accompanying psychoneurological symptoms. However, the patient presented with other symptoms, including diabetes mellitus, hearing loss, abnormal lactate levels, ischaemic lesions on head MRI, and left ventricular hypertrophy. By identifying a mutation in the MT-TL1 gene and conducting a muscle biopsy, the diagnosis of MELAS syndrome was definitively confirmed.
Trade Shocks, Labour Markets and Migration in the First Globalisation
Authors: Bräuer Richard , Kersting Felix
Published: September 2023

This paper studies the economic and political effects of a large trade shock in agriculture—the grain invasion from the Americas—in Prussia during the first globalisation (1870–913). We show that this shock led to a decline in the employment rate and overall income. However, we do not observe declining per capita income and political polarisation, which we explain by a strong migration response. Our results suggest that the negative and persistent effects of trade shocks we see today are not a universal feature of globalisation, but depend on labour mobility. For our analysis, we digitise data from Prussian industrial and agricultural censuses on the county level and combine them with national trade data at the product level. We exploit the cross-regional variation in cultivated crops within Prussia and instrument with Italian and United States trade data to isolate exogenous variation.
Divergence in the internal genital morphology of females and correlated divergence in male intromittent structures among populations of a millipede
Authors: Sloan Nadia S , Kennington W Jason , Simmons Leigh W
Published: September 2023

Our understanding of genital evolution comes largely from studies of male genitalia. Females have received far less attention because of the difficulties inherent in quantifying the shapes of their internal genital structures. Here we combine advances in micro-computed tomography with a new landmark free method of quantifying three-dimensional trait shape, to document patterns of divergence in female genital shape, and the correlated divergence of male genitalia among populations of the millipede Antichiropus variabilis. We used single-nucleotide polymorphisms to estimate levels of neutral genetic divergence among seven populations of millipede. Genetic divergence was high and correlated with geographic distance. Comparing phenotypic divergence in genital shape to neutral genetic divergence, we found that genital shape for both females and males has diverged more than would be expected from random drift, consistent with a pattern of directional selection. While there was significant covariation between female and male genital shape across populations, the magnitude of divergence in genital shape between the sexes was not correlated. Our results demonstrate the utility of using three-dimensional scanning technologies to examine female genital traits and add to a small but growing number of studies showing that like male genitalia, female genitalia can be under strong directional selection.
Melatonin retards leaf senescence by modulating phytohormone metabolism in stored Chinese flowering cabbage
Authors: Li Chenxiang , Shen Xuemeng , Fan Zhongqi , Chen Jianye , Tao Nengguo , Tan Xiaoli
Published: September 2023

This paper was conducted to explore the effects of melatonin (MT) on the senescence of stored Chinese flowering cabbage and the potential modulatory mechanisms involved. The physiological findings demonstrated that MT successfully reduced chlorophyll loss and improved the photochemical effectiveness of cabbage leaves. In addition, MT decreased the transcription of senescence-associated genes (BrSAG12) and genes responsible for chlorophyll breakdown. Transcriptome analysis showed that MT-regulated genes were enriched in oxidative phosphorylation, hormone metabolism and signal transduction, and MT treatment reduced the high expression of genes linked to generation of reactive oxygen species (ROS), energy metabolism, phytohormone (abscisic acid (ABA), ethylene (ET), and jasmonic acid (JA)) biological synthesis and signal transduction while promoting the activation of genes related to scavenging ROS, energy biosynthesis and plant–pathogen interactions. We emphasized the examination of the potential interaction between phytohormone metabolism and MT. The results showed that the application of MT decreased ABA, ET, and JA levels as well as the expression of their biosynthesis genes, concurrently maintaining higher expression of cytokinin, auxin and gibberellin biosynthetic genes and lower expression of degradation genes. Regulatory networks of transcription factors (TFs) and genes related to ABA, ET and JA metabolism showed that TFs such as DNA-binding One Zinc Finger 5.7 (DOF5.7), WRKY40, and homeobox-leucine zipper protein-16 (ATHB-16) might play important transcriptional regulatory roles in mediating MT postponed leaf senescence. Taken together, these findings suggested that the postponed senescence of cabbage treated with MT might be ascribed to the regulated oxidative phosphorylation, energy, phytohormone metabolism, and transcription factors.
Mid-Life Vascular Risk and Rate of Physical Function Decline Among Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Skow Laura F , Sharrett A Richey , Gottesman Rebecca F , Coresh Josef , Deal Jennifer A , Palta Priya , Sullivan Kevin J , Griswold Michael E , Schrack Jennifer A , Windham B Gwen
Published: September 2023

Background

Physical function and its decline in older age may be connected to treatable vascular risk factors in mid-life. This study aimed to evaluate whether these factors affect the underlying rate of decline.

Methods

This prospective cohort included 5 481 older adults aged 67–91 in the Atherosclerosis Risk in Communities Study (mean [standard deviation {SD}] age = 75.8 [5.0], 58% women, 21% Black race) without a history of stroke. The main outcome was the rate of Short Physical Performance Battery (SPPB) decline over a median late-life follow-up of 4.8 years. Primary mid-life (aged 45–64) exposures were Visit 1 hypertension (>140/90 mm Hg or treatment), diabetes (>126 mg/dL or treatment), high cholesterol (>240 mg/dL or treatment), and smoking, and number of decades of vascular risk exposure across Visits 1–4.

Results

The average adjusted rate of SPPB decline (points per 5 years) for older adults was −0.79 (confidence interval [CI]: −0.87, 0.71) and was accelerated by mid-life hypertension (+57% decline vs normotension: additional decline of −0.47, 95% CI: −0.64, −0.30), diabetes (+73% decline vs no diabetes: additional decline of −0.67, 95% CI: −1.09, −0.24), elevated systolic blood pressure (+17% decline per SD: −0.16, 95% CI: −0.23, −0.10), and elevated fasting blood glucose (+16% decline per SD: −0.015, 95% CI: −0.24, −0.06). Each decade greater mid-life exposure to hypertension (+32% decline: −0.93, 95% CI: −1.25, −0.61) and diabetes (+35% decline: −1.03, 95% CI: −1.68, −0.38) was associated with faster SPPB decline.

Conclusions

Mid-life control of blood pressure and diabetes may offset aging-related functional decline.
Src is a target molecule of mannose against pancreatic cancer cells growth in vitro & in vivo
Authors: Xie Jianhao , Wu Shengjie , Liao Wenfeng , Ning Jingru , Ding Kan
Published: September 2023

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Mannose, a common monosaccharide taken up by cells through the same transporters as glucose, has been shown to induce growth retardation and enhance cell death in response to chemotherapy in several cancers, including PDAC. However, the molecular targets and mechanisms underlying mannose’s action against PDAC are not well understood. In this study, we used an integrative approach of network pharmacology, bioinformatics analysis, and experimental verification to investigate the pharmacological targets and mechanisms of mannose against PDAC. Our results showed that the protein Src is a key target of mannose in PDAC. Additionally, computational analysis revealed that mannose is a highly soluble compound that meets Lipinski’s rule of five and that the expression of its target molecules is correlated with survival rates and prognosis in PDAC patients. Finally, we validated our findings through in vitro and in vivo experiments. In conclusion, our study provides evidence that mannose plays a critical role in inhibiting PDAC growth by targeting Src, suggesting that it may be a promising therapeutic candidate for PDAC.
The Effectiveness and Safety of First-Line Thioguanine in Thiopurine-Naïve Inflammatory Bowel Disease Patients
Authors: Crouwel Femke , Bayoumy Ahmed B , Mulder Chris J J , Peters Job H C , Boekema Paul J , Derijks Luc J J , de Boer Sybrand Y , van de Meeberg Paul C , Ahmad Ishfaq , Buiter Hans J C , de Boer Nanne K
Published: September 2023

Background

Currently thioguanine is solely used as treatment for inflammatory bowel disease after azathioprine and/or mercaptopurine failure. This study aimed to determine the safety, effectiveness, and 12-month drug survival of thioguanine in thiopurine-naïve patients with inflammatory bowel disease.

Methods

A retrospective cohort study was performed in thiopurine-naïve patients with inflammatory bowel disease treated with thioguanine as first thiopurine derivate. Clinical effectiveness was defined as the continuation of thioguanine without the (re)initiation of concurrent biological therapy, systemic corticosteroids, or a surgical intervention. All adverse events were categorized by the Common Terminology Criteria for Adverse Events.

Results

A total of 114 patients (male 39%, Crohn’s disease 53%) were included with a median treatment duration of 25 months and a median thioguanine dosage of 20 mg/d. Clinical effectiveness at 12 months was observed in 53% of patients, and 78% of these responding patients remained responsive until the end of follow-up. During the entire follow-up period, 26 patients were primary nonresponders, 8 had a secondary loss of response, and 11 patients were unable to cease therapy with systemic corticosteroids within 6 months and were therefore classified as nonresponders. After 12 months, thioguanine was still used by 86% of patients. Fifty (44%) patients developed adverse events (grade 1 or 2) and 9 (8%) patients ceased therapy due to the occurrence of adverse events. An infection was documented in 3 patients, none of them requiring hospitalization and pancytopenia occurred in 2 other patients. No signs of nodular regenerative hyperplasia or portal hypertension were observed.

Conclusions

At 12 months, first-line thioguanine therapy was clinically effective in 53% of thiopurine-naïve inflammatory bowel disease patients with an acceptable safety profile.
Learning river water quality models by l1-weighted regularization
Authors: Nho Hào Dinh , Xuan Hiep Duong , Quy Muoi Pham
Published: September 2023

We investigate the problem of learning a water quality model (BOD-DO model) from given data. Assuming that all parameters in the model are constants, we reformulate the problem as a system of linear equations for the unknown terms. Since in practice the system is often under-determined or over-determined and the observed data are noisy, we use an $l^{1}$-weighted regularization method to find a stable approximate solution. Then, Nesterov’s algorithm is used to solve the regularized problem. Learning models with variable coefficients are also discussed. Numerical examples show that our approach works well with noisy data and has the ability to learn the BOD-DO model.
Interpretable model learning in variational imaging: a bilevel optimization approach
Authors: De los Reyes Juan Carlos , Villacís David
Published: September 2023

In this paper, we investigate the use of bilevel optimization for model learning in variational imaging problems. Bilevel learning is an alternative approach to deep learning methods, which leads to fully interpretable models. However, it requires a detailed analytical insight into the underlying mathematical model. We focus on the bilevel learning problem for total variation models with spatially- and patch-dependent parameters. Our study encompasses the directional differentiability of the solution mapping, the derivation of optimality conditions, and the characterization of the Bouligand subdifferential of the solution operator. We also propose a two-phase trust-region algorithm for solving the problem and present numerical tests using the CelebA dataset.
Comparison of Two Clinical Laboratory Assays for Measuring Serum Adalimumab and Antibodies to Adalimumab
Authors: Jain Dharmendra , Pido Mary Therese J , Delgado Julio C , Willrich Maria Alice V , Lázár-Molnár Eszter
Published: September 2023

Background

Adalimumab is a fully human monoclonal antibody developed against tumor necrosis factor (TNF), used for the treatment of autoimmune and chronic inflammatory diseases. Immunogenicity to this drug may lead to therapeutic failure. Various laboratory assays are used for measuring serum adalimumab and anti-drug antibodies (ADA) to adalimumab, for therapeutic monitoring and evaluation of clinical non-responsiveness. This study compared the performance of 2 clinical assays used by different reference laboratories.

Methods

In total, 120 residual clinical samples were tested at both laboratories. A sandwich ELISA for adalimumab detecting free drug and a bridging ELISA capable of detecting both free and bound ADA were performed at the Mayo Clinic. A functional cell-based reporter gene assay (RGA) was used at ARUP Laboratories for measuring bioactive serum drug concentrations, and neutralizing ADA.

Results

Seventy-eight samples had measurable concentrations of adalimumab by both methods and yielded a correlation coefficient r = 0.93, slope = 0.886, and intercept = 0.950. Overall agreement of 92.5% was observed between the assays, with most discrepant drug results being attributed to a higher positivity rate with ELISA (8/9). One outlier positive with RGA and negative with ELISA was confirmed by LC-MS/MS to be attributed to infliximab. Overall agreement of 79.2% was observed between the ADA assays. Differences in ADA results may be due to the bridging ELISA detecting total ADA (free, drug-bound, neutralizing, and non-neutralizing), while RGA detects free, neutralizing ADA only.

Conclusions

Although the assays are fundamentally different, the results show significant concordance between the clinically validated tests performed in different laboratories.
Prediction models using artificial intelligence and longitudinal data from electronic health records: a systematic methodological review
Authors: Carrasco-Ribelles Lucía A , Llanes-Jurado José , Gallego-Moll Carlos , Cabrera-Bean Margarita , Monteagudo-Zaragoza Mònica , Violán Concepción , Zabaleta-del-Olmo Edurne
Published: September 2023

Objective

To describe and appraise the use of artificial intelligence (AI) techniques that can cope with longitudinal data from electronic health records (EHRs) to predict health-related outcomes.

Methods

This review included studies in any language that: EHR was at least one of the data sources, collected longitudinal data, used an AI technique capable of handling longitudinal data, and predicted any health-related outcomes. We searched MEDLINE, Scopus, Web of Science, and IEEE Xplorer from inception to January 3, 2022. Information on the dataset, prediction task, data preprocessing, feature selection, method, validation, performance, and implementation was extracted and summarized using descriptive statistics. Risk of bias and completeness of reporting were assessed using a short form of PROBAST and TRIPOD, respectively.

Results

Eighty-one studies were included. Follow-up time and number of registers per patient varied greatly, and most predicted disease development or next event based on diagnoses and drug treatments. Architectures generally were based on Recurrent Neural Networks-like layers, though in recent years combining different layers or transformers has become more popular. About half of the included studies performed hyperparameter tuning and used attention mechanisms. Most performed a single train-test partition and could not correctly assess the variability of the model’s performance. Reporting quality was poor, and a third of the studies were at high risk of bias.

Conclusions

AI models are increasingly using longitudinal data. However, the heterogeneity in reporting methodology and results, and the lack of public EHR datasets and code sharing, complicate the possibility of replication.

Registration

PROSPERO database (CRD42022331388).