bluuebunny/crossref_metadata_2025 huggingface dataset:
Independent age estimates resolve the controversy of ancient human footprints at White Sands
Authors: Pigati Jeffrey S. , Springer Kathleen B. , Honke Jeffrey S. , Wahl David , Champagne Marie R. , Zimmerman Susan R. H. , Gray Harrison J. , Santucci Vincent L. , Odess Daniel , Bustos David , Bennett Matthew R.
Published: October 2023

Human footprints at White Sands National Park, New Mexico, USA, reportedly date to between ~23,000 and 21,000 years ago according to radiocarbon dating of seeds from the aquatic plant
Ruppia cirrhosa
. These ages remain controversial because of potential old carbon reservoir effects that could compromise their accuracy. We present new calibrated
14
C ages of terrestrial pollen collected from the same stratigraphic horizons as those of the
Ruppia
seeds, along with optically stimulated luminescence ages of sediments from within the human footprint–bearing sequence, to evaluate the veracity of the seed ages. The results show that the chronologic framework originally established for the White Sands footprints is robust and reaffirm that humans were present in North America during the Last Glacial Maximum.
Structure of a ribonucleotide reductase R2 protein radical
Authors: Lebrette Hugo , Srinivas Vivek , John Juliane , Aurelius Oskar , Kumar Rohit , Lundin Daniel , Brewster Aaron S. , Bhowmick Asmit , Sirohiwal Abhishek , Kim In-Sik , Gul Sheraz , Pham Cindy , Sutherlin Kyle D. , Simon Philipp , Butryn Agata , Aller Pierre , Orville Allen M. , Fuller Franklin D. , Alonso-Mori Roberto , Batyuk Alexander , Sauter Nicholas K. , Yachandra Vittal K. , Yano Junko , Kaila Ville R. I. , Sjöberg Britt-Marie , Kern Jan , Roos Katarina , Högbom Martin
Published: October 2023

Aerobic ribonucleotide reductases (RNRs) initiate synthesis of DNA building blocks by generating a free radical within the R2 subunit; the radical is subsequently shuttled to the catalytic R1 subunit through proton-coupled electron transfer (PCET). We present a high-resolution room temperature structure of the class Ie R2 protein radical captured by x-ray free electron laser serial femtosecond crystallography. The structure reveals conformational reorganization to shield the radical and connect it to the translocation path, with structural changes propagating to the surface where the protein interacts with the catalytic R1 subunit. Restructuring of the hydrogen bond network, including a notably short O–O interaction of 2.41 angstroms, likely tunes and gates the radical during PCET. These structural results help explain radical handling and mobilization in RNR and have general implications for radical transfer in proteins.
Ancient DNA genomics and the renaissance of herbaria
Authors: Burbano Hernán A. , Gutaker Rafal M.
Published: October 2023

Herbaria are undergoing a renaissance as valuable sources of genomic data for exploring plant evolution, ecology, and diversity. Ancient DNA retrieved from herbarium specimens can provide unprecedented glimpses into past plant communities, their interactions with biotic and abiotic factors, and the genetic changes that have occurred over time. Here, we highlight recent advances in the field of herbarium genomics and discuss the challenges and opportunities of combining data from modern and time-stamped historical specimens. We also describe how integrating herbarium genomics data with other data types can yield substantial insights into the evolutionary and ecological processes that shape plant communities. Herbarium genomic analysis is a tool for understanding plant life and informing conservation efforts in the face of dire environmental challenges.
Pregnancy programs the brain for mothering
Authors: McCarthy Margaret M.
Published: October 2023

Progesterone and estrogen exert separate effects on the brains of pregnant mice
A metabolic role for CD47 in pancreatic β cell insulin secretion and islet transplant outcomes
Authors: Ghimire Kedar , Kale Atharva , Li Jennifer , Julovi Sohel M. , O’Connell Philip , Grey Shane T. , Hawthorne Wayne J. , Gunton Jenny E. , Rogers Natasha M.
Published: October 2023

Diabetes is a global public health burden and is characterized clinically by relative or absolute insulin deficiency. Therapeutic agents that stimulate insulin secretion and improve insulin sensitivity are in high demand as treatment options. CD47 is a cell surface glycoprotein implicated in multiple cellular functions including recognition of self, angiogenesis, and nitric oxide signaling; however, its role in the regulation of insulin secretion remains unknown. Here, we demonstrate that CD47 receptor signaling inhibits insulin release from human as well as mouse pancreatic β cells and that it can be pharmacologically exploited to boost insulin secretion in both models. CD47 depletion stimulated insulin granule exocytosis via activation of the Rho GTPase Cdc42 in β cells and improved glucose clearance and insulin sensitivity in vivo. CD47 blockade enhanced syngeneic islet transplantation efficiency and expedited the return to euglycemia in streptozotocin-induced diabetic mice. Further, anti-CD47 antibody treatment delayed the onset of diabetes in nonobese diabetic (NOD) mice and protected them from overt diabetes. Our findings identify CD47 as a regulator of insulin secretion, and its manipulation in β cells offers a therapeutic opportunity for diabetes and islet transplantation by correcting insulin deficiency.
Recyclable CRISPR/Cas9-mediated gene disruption and deletions in
Histoplasma
Authors: Joehnk Bastian , Ali Nebat , Voorhies Mark , Walcott Keith , Sil Anita
Published: October 2023

Targeted gene disruption is challenging in the dimorphic fungal pathogen
Histoplasma
due to the low frequency of homologous recombination. Transformed DNA is either integrated ectopically into the genome or maintained extrachromosomally by
de novo
addition of telomeric sequences. Based on a system developed in
Blastomyces
, we adapted a CRISPR/Cas9 system to facilitate targeted gene disruption in
Histoplasma
with high efficiency. We express a codon-optimized version of Cas9 as well as guide RNAs from a single ectopic vector carrying a selectable marker. Once the desired mutation is verified, one can screen for isolates that have lost the Cas9 vector by simply removing the selective pressure. Multiple mutations can then be generated in the same strain by retransforming the Cas9 vector carrying different guides. We used this system to disrupt a number of target genes including
RYP2
and
SRE1
, where loss-of-function mutations could be monitored visually by colony morphology or color, respectively. Interestingly, expression of two guide RNAs targeting the 5′- and 3′-ends of a gene allowed isolation of deletion mutants where the sequence between the guide RNAs was removed from the genome. Whole-genome sequencing showed that the frequency of off-target mutations associated with the Cas9 nuclease was negligible. Finally, we increased the frequency of gene disruption by using an endogenous
Histoplasma
regulatory sequence to drive guide RNA expression. These tools transform our ability to generate targeted mutations in
Histoplasma
.

IMPORTANCE

Histoplasma
is a primary fungal pathogen with the ability to infect otherwise healthy mammalian hosts, causing systemic and sometimes life-threatening disease. Thus far, molecular genetic manipulation of this organism has utilized RNA interference, random insertional mutagenesis, and a homologous recombination protocol that is highly variable and often inefficient. Targeted gene manipulations have been challenging due to poor rates of homologous recombination events in
Histoplasma
. Interrogation of the virulence strategies of this organism would be highly accelerated by a means of efficiently generating targeted mutations. We have developed a recyclable CRISPR/Cas9 system that can be used to introduce gene disruptions in
Histoplasma
with high efficiency, thereby allowing disruption of multiple genes.
Saccular posterior cerebral artery aneurysm encased within a lipoma
Authors: Chin Calvin Wing Hang , Kweh Barry Ting Sheen , Gonzalvo Augusto
Published: October 2023

We present a case of a man in his 80s with an incidental posterior cerebral artery aneurysm encased within a lipoma. The literature surrounding the incidence and intricate relationship of lipomas to cerebral aneurysms is reviewed. Lipomas are proposed to be derived from maldifferentiated subarachnoid space. For this reason, lipomas are often associated with vascular malformations and may develop in conjunction with vascular malformations such as cerebral aneurysms. Hypothesised theories include the impediment of smooth muscle nutrient diffusion and the secretion of factors that weaken the arterial wall thereby predisposing to aneurysm formation. When lipomas neighbour cerebral vasculature, careful evaluation of the adjacent vessels should be conducted.
Automatic graph construction and Exploring different types of LSTMs for Asian Hindi languages for Medical review Sentiment Analysis
Authors: kumari Rani , Sah Dinesh Kumar , Cengiz Korhan , Ivković Nikola , Balaji Prasanalakshmi
Published: October 2023

Sentiment Analysis (SA) of medical reviews is crucial for improving healthcare outcomes. However, analyzing sentiment in low-resource languages such as Asian Hindi presents significant challenges. In this study, we propose an automatic graph construction approach to extract relevant features from medical reviews in Asian Hindi languages. We explore different types of Long Short-Term Memory (LSTMs), including traditional LSTMs, bidirectional LSTMs, and attention-based LSTMs, to classify the sentiment of medical reviews. Our proposed approach uses attention-based LSTM architecture and pre-trained Word2Vec embeddings to achieve high accuracy. We compare the proposed approach with existing models using various evaluation metrics, including accuracy, precision, recall, and F1-score. The results demonstrate that our proposed approach outperforms all existing models in terms of accuracy, achieving an accuracy score of 81%. These findings could have implications for improving healthcare outcomes by enabling better monitoring of patient feedback and identifying areas for improvement in medical services.
Sum Rate Optimization for MIMO Multicasting Network with Active IRS
Authors: Li Ping , Bian Jinhong
Published: October 2023

This paper considers a multiple-input multiple-output (MIMO) multicasting system aided by the intelligent reflecting surface (IRS). We aim to maximize the sum information rate via jointly designing the transmit precoding matrix and the reflecting coefficient (RC) matrix, subject to the transmit power constrains of the Tx and IRS. To tackle the nonconvex problem, we recast the original problem into an equivalent formulation by using some important facts about matrices and proposed a block coordinate descent (BCD) method to optimize the variables. Finally, simulation results validate the effectiveness of active IRS in enhancing the rate performance.
THD Reduction of Improved Single Source MLI Using Upgraded Black Widow Optimization Algorithm
Authors: Mohanty Rupali , Chatterjee Debashis , Mohanty Satyajit , Dhanamjayulu C. , Khan Baseem
Published: October 2023

An upgraded Black Widow Optimization algorithm for obtaining the ideal switching angles of a reduced structure multilevel inverter is proposed in this paper with minimum voltage THD. The conventional BWO algorithm has been modified and proposed to solve the THD minimization problem with faster convergence rate, lesser tuning variables, and lesser number of equations than the other existing nature inspired algorithms. The reduced structure MLI is designed with three asymmetrical DC voltage sources of ratio 1 : 2 : 4 to generate 15-level output voltage which requires reduced number of switching devices in comparison with the existing topologies of equivalent voltage level. The asymmetrical DC voltage sources to the MLI are derived from a single DC voltage source using a multisecondary winding DC-DC converter in order to provide the isolation between the load side and source side. The proposed modified BWO algorithm reduces the complexity of solving the nonlinear equations to achieve the best result by avoiding the local optima. To verify the effectiveness of the upgraded BWO algorithm, the optimization problem for three phase fifteen level MLI has been solved using the genetic algorithm, BFO algorithm, and PSO algorithm. The results for the above three applied algorithms are compared with the upgraded BWO and presented. The proposed algorithm has minimized the output voltage THD to 1.83% at 0.88 modulation index. The developed scheme has been corroborated with the help of MATLAB simulation and the results have been verified through a hardware model developed in laboratory.
TCN1 Expression Is Increased in Asthma
Authors: Xu Changyi , Du Lijuan , Guo Yubiao , Liang Yuxia
Published: October 2023

Introduction: Asthma is a chronic disease that affects populations worldwide. The purpose of this study was to investigate the expression of TCN1 in sputum and its correlation with inflammation and lung function in asthma. Methods: We recruited 141 subjects, detected TCN1 mRNA level by quantitative reverse transcription polymerase chain reaction, detected TCN1 protein expression by Western blot, detected TCN1 protein level by enzyme-linked immunosorbent assay, and analyzed the correlation between TCN1 and fraction of exhaled nitric oxide (FeNO), IgE, EOS%, lung functions, and some Th2 cytokines. The diagnostic value of TCN1 was evaluated by receiver operating characteristics curve. The expression of TCN1 was further confirmed by human bronchial epithelial cell in vitro. Results: Compared with the health group, the expression of TCN1 in induced sputum cells increased in asthma group and was correlated with FeNO, IgE, and EOS%. TCN1 level was also elevated in the induced sputum supernatant of asthma patients. The protein level of TCN1 in induced sputum supernatant was correlated with FeNO, IgE and PC-20, forced expiratory volume in the first second (FEV1)%pred, FEV1/FVC, and some cytokines (IL-4, IL-5, IL-10, IL-13, MUC5AC). TCN1 was also differentially expressed in patients with different severity of asthma. Four weeks after ICS treatment, the expression of TCN1 in induced sputum supernatant increased. In vitro, the protein level of TCN1 in human bronchial epithelial cells’ supernatant increased after stimulated with IL-4 and IL-13. Conclusion: The expression of TCN1 was increased in asthma patients’ sputum, and was positively correlated with some inflammatory markers, negatively correlated with lung function. TCN1 may be used as a potential biomarker for the diagnosis and treatment of asthma.
A Retrospective Cohort Study Characteristics of Chest X-Ray Findings in COVID-19 Patients that Presented to a Tertiary Care Facility in Dubai: Can a Severe Radiological Appearance Predict Clinical Outcome?
Authors: Alhaddad Duaa Yusuf , Ahmed Ayeda , Aldashtei Maryam , Abedzadeh Ayoub , Iqbal Shaikh Sayeed , Armaghan Yaser , AlNajjar Firas
Published: October 2023

Aim: We aimed to describe the most prominent features of COVID-19 on the chest X-ray (CXR) and to classify them using the radiographic assessment of lung edema (RALE) score. Furthermore, we aimed to correlate the RALE scores with clinically significant outcomes namely intensive care unit (ICU) admission and intubation from the emergency versus during hospital stay. In-hospital, death was studied as a secondary endpoint for severe RALE score. Materials and Methods: A retrospective cohort study was conducted on patients presenting to the emergency department (ED) of a tertiary hospital between the periods of March 2020 to August 2020. Included patients were symptomatic, COVID-19 positive by nasopharyngeal real-time polymerase chain reaction (RT-PCR), who also performed an initial CXR in the ED. Two experienced radiologists interpreted the CXRs and categorized them using RALE score into normal mild, moderate, and severe for further correlation with clinical endpoints. Results: From the 404 CXRs, most were categorized as mild and characteristically CXRs had bilateral lower and mid-zone ground-glass opacities. The frequency of intubation and ICU admission increased as the RALE score worsened with a statistically significant p value of <0.001. Severe CXR required earlier intervention and was found to have the highest proportion of mortality. Discussion: The RALE score has shown to be a highly reliable indicator for worse outcome in patients with acute respiratory distress syndrome. While RT-PCR has variable sensitivities, CXR has demonstrated to have characteristic findings and higher RALE scores having a significant correlation for intubation and ICU admission in this research. Conclusion: The prognostic utility of CXR in COVID-19 has been found to be of statistical significance for intubation and ICU admission. CXR is a simple, portable, and easy-to-disinfect method of evaluation that can be invaluable in determining timely intervention and disposition of patients expecting deterioration.
Clinical Significance of the TK1-Specific Activity in the Early Detection of Ovarian Cancer
Authors: Osredkar Joško , Jagarlamudi Kiran Kumar , Cviič Diana , Škof Erik , Cvjetićanin Branko , Zore Andrej , Lukanović David , Eriksson Staffan , Meglič Leon
Published: October 2023

Introduction: Ovarian cancer is the eighth most common cause of cancer death in women. One of the major concerns is almost two-thirds of cases are typically diagnosed in the late stage as the symptoms are unspecific in the early stage of ovarian cancer. It is known that the combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone. That is why, the aim of the study was to investigate whether the TK1-specific activity (TK1 SA) could function as a complement marker for early-stage diagnosis of ovarian cancer. Methods: The study included a set of 198 sera consisting of 134 patients with ovarian tumors (72 benign and 62 malignant) and 64 healthy age-matched controls. The TK1 SA was determined using TK1 activity by TK-Liaison and TK1 protein by AroCell TK 210 ELISA. Further, CA 125, HE4, as well as risk of ovarian malignancy algorithm index were also determined in the same set of clinical samples. Results: The TK1 SA was significantly different between healthy compared to ovarian cancer patients (p < 0.0001). Strikingly, TK1 SA has higher sensitivity (55%) compared to other biomarkers in the detection of benign ovarian tumors. Further, the highest sensitivity was achieved by the combination of TK1 SA with CA 125 and HE4 for the detection of benign tumors as well as malignant ovarian tumors (72.2% and 88.7%). In addition, TK1 SA could significantly differentiate FIGO stage I/II from stage III/IV malignancies (p = 0.026). Follow-up of patients after surgery and chemotherapy showed a significant difference compared to TK1 SA at the time of diagnosis. Conclusions: These results indicate that TK1 SA is a promising blood-based biomarker that could complement CA 125 and HE4 for the detection of early stages of ovarian cancer.
Ruptured Gastroduodenal Artery Pseudoaneurysms as a Complication of Pancreatitis
Authors: Ghazanfar Haider , Jyala Abhilasha , Kandhi Sameer Datta , Shin Dongmin , Samsuddoha Kazi , Patel Harish
Published: October 2023

Visceral artery pseudoaneurysms is a known vascular complication of pancreatitis that can lead to life-threatening hemorrhages with a high mortality rate if left untreated. We present a case of ruptured gastroduodenal artery pseudoaneurysm in a 68-year-old male with acute pancreatitis presenting with fatal gastrointestinal and retroperitoneal bleeding that was successfully managed with endovascular coil embolization of the involved vasculature. Patients with hemorrhagic pancreatitis or those presenting with unexplained retroperitoneal or gastrointestinal bleeding in the setting of pancreatitis with an unexplained drop in hematocrit or sudden expansion of pancreatic fluid collection should be screened in a timely manner for pseudoaneurysm using CT angiogram of the abdomen, which is the gold standard imaging modality to identify pseudoaneurysms. Once pseudoaneurysm is diagnosed, it should be treated immediately. Endovascular treatment options are now favored over surgical options in most cases.
Prevalence and Risk Factors of Cerebral Small Vessel Disease from a Population-Based Cohort in China
Authors: Yang Yingying , Cai Xueli , Zhou Mengyuan , Chen Yiyi , Pi Jingtao , Zhao Mengxi , Shi Yulu , Wang Suying , Jing Jing , Chen Weiqi , Meng Xia , Wang Yongjun , Pan Yuesong , Wang Yilong
Published: October 2023

Introduction: Cerebral small vessel disease (CSVD) is a significant burden of morbidity and mortality among elderly people around the world. Epidemiological data with complete CSVD evaluations and a large sample size in the general population are still limited. Methods: Community-dwelling residents in Lishui city in China from the cross-sectional survey of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study were included in this study from 2017 to 2019. All participants underwent 3 Tesla brain magnetic resonance images to assess CSVD imaging markers. Demographic and risk factor data were collected. The general and age-specific prevalence of lacune, confluent white matter hyperintensity (WMH), moderate-severe enlarged perivascular spaces (EPVS), cerebral microbleed (CMB), and total CSVD score (an ordinal scale from 0 to 4, counting the presence of four imaging markers of CSVD) was evaluated. Associations between vascular risk factors and these markers were analyzed by multivariable logistic regression. Results: A total of 3,063 participants were enrolled. The mean age was 61.2 years and 46.5% were men. The most prevalent CSVD marker was confluent WMH (16.7%), followed by CMB (10.2%), moderate-severe EPVS in the basal ganglia (BG-EPVS) (9.8%), and lacune (5.6%). 30.5% of the participants have at least one of the four markers (total CSVD score ≥1 points). The prevalence of CSVD markers increases as age increases. Age and hypertension were independent risk factors for four CSVD markers and the total CSVD score. Conclusions: In this Chinese cohort with community-based adults aged 50–75 years, our findings showed a prevalence of 30.5% for CSVD. The most prevalent CSVD marker was confluent WMH, followed by CMB, moderate-severe BG-EPVS, and lacune. The risk factors for CSVD must be strictly screened and controlled in adults living in the community.
Clinicopathological Characteristics and Prognosis of Lupus Nephritis Patients with Acute Kidney Injury
Authors: Li Suchun , Luo Qimei , Fan Yuting , Zhao Chen , Huang Fengxian , Xia Xi , Chen Wei
Published: October 2023

Introduction: Acute kidney injury (AKI) is common in lupus nephritis (LN) and a risk factor for chronic kidney failure. Here, we aimed to assess the characteristics and prognosis of LN patients with AKI. Methods: AKI and AKI severity stages in LN patients were defined by the Kidney Disease Improving Global Outcomes (KDIGO) classification. Long-term renal outcomes and patient mortality between different stages of AKI were compared by Cox regression analysis. Results: Of 1272 LN patients, 225 (17.69%) had AKI and 72 (5.66%) were AKI stage 3. Compared with the non-AKI group, the proportion of male patients was significantly higher in the AKI group (p = 0.002). In addition, there were markedly higher proportions of hematologic system damage, more severe renal manifestations, and higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores in the AKI group than in the non-AKI group. The active and chronic lesions in renal biopsy were significantly higher in LN patients with AKI than those without AKI. During a median follow-up of 53 months, Kaplan-Meier curve showed that LN patients with AKI stage 3 had significantly poorer long-term renal outcomes (p = 0.002) and patient survival (p < 0.001) than those without AKI. Furthermore, AKI stage 3, but not stage 1 or 2 was significantly associated with adverse renal outcomes (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.01–6.28, p = 0.048) and all-cause mortality (HR = 2.80, 95% CI: 1.18–6.61, p = 0.019) in LN patients. In patients with AKI, increased baseline serum creatinine and severe glomerular sclerosis were independent risk factors for worse renal outcomes, while higher blood pressure, increased baseline serum creatinine, and anti-Sjogren’s syndrome A positivity could indicate poor survival. Discussion: LN patients with AKI stage 3, but not stages 1 and 2, have poorer long-term renal outcomes and patient survival. Our study demonstrates the importance of early identification and management of AKI in LN patients.
Selected β-Glucans Act as Immune-Training Agents by Improving Anti-Mycobacterial Activity in Human Macrophages: A Pilot Study
Authors: Braian Clara , Karlsson Lovisa , Das Jyotirmoy , Lerm Maria
Published: October 2023

Epigenetic reprogramming of innate immune cells by β-glucan in a process called trained immunity leads to an enhanced host response to a secondary infection. β-Glucans are structural components of plants, algae, fungi, and bacteria and thus recognized as non-self by human macrophages. We selected the β-glucan curdlan from Alcaligenes faecalis, WGP dispersible from Saccharomyces cerevisiae, and β-glucan-rich culture supernatant of Alternaria and investigated whether they could produce trained immunity effects leading to an increased control of virulent Mycobacterium tuberculosis. We observed a significant M. tuberculosis growth reduction in macrophages trained with curdlan and Alternaria, which also correlated with increased IL-6 and IL-1β release. WGP dispersible-trained macrophages were stratified into “non-responders” and “responders,” according to their ability to control M. tuberculosis, with “responders” producing higher IL-6 levels. The addition of neutrophils to infected macrophage cultures further enhanced macrophage control of virulent M. tuberculosis, but not in a stimuli-dependent manner. Pathway enrichment analysis of DNA methylome data also highlighted hypomethylation of genes in pathways associated with signaling and cellular reorganization and motility, and “responders” to WGP training were enriched in the interferon-gamma signaling pathway. This study adds evidence that certain β-glucans show promise as immune-training agents.
Immunotherapy for Gestational Trophoblastic Neoplasia: A New Paradigm
Authors: Baas Inge O. , Westermann Anneke M. , You Benoit , Bolze Pierre-Adrien , Seckl Michael , Ghorani Ehsan
Published: October 2023

Background: Immune checkpoint immunotherapy (CPI) targeting programmed cell death 1 (PD-1)/ligand (PD-L1) has been shown to be an effective treatment for gestational trophoblastic neoplasia (GTN). This includes those with multidrug resistance, ultra-high-risk disease, and epithelioid trophoblastic tumour/placental site trophoblastic tumour subtypes that are inherently chemotherapy resistant, but there is also emerging evidence in low-risk disease. Objectives: We set out to generate an overview of the current data supporting the use of CPI for GTN in both high-risk and low-risk disease and to consider future research goals and directions in order to implement CPI in current treatment guidelines. Methods: We identified and reviewed the published data on the use of CPI agents in GTN. Outcome: 133 patients were identified who had been treated with CPI for GTN with pembrolizumab (23), avelumab (22), camrelizumab (57), toripalimab (15), or other anti-PD-1 agents (16), of whom 118 had high-risk diseases, relapse or multi-drug resistant disease, and 15 low-risk diseases. Overall 85 patients achieved complete remission, 77 (of 118) with high-risk disease, and 8 (of 15) with low-risk disease. 1 patient with complete remission in the high-risk group developed a relapse 22 months after anti-PD-1 treatment had been stopped. Treatment was generally well tolerated across studies. Conclusions and Outlook: The majority of high-risk patients (77/118) treated with CPI are cured and this is particularly relevant amongst those with chemotherapy resistant disease who otherwise have very limited treatment options. Priorities for future research include determining whether these agents have a role earlier in the disease course, the utility of combination with chemotherapy, and effects on future fertility. Treatment availability remains a concern due to the high price of these agents.
Green Tea-Derived Catechins Suppress the Acid Productions of Streptococcus mutans and Enhance the Efficiency of Fluoride
Authors: Han Sili , Washio Jumpei , Abiko Yuki , Zhang Linglin , Takahashi Nobuhiro
Published: October 2023

Green tea-derived catechins, which can be divided into galloylated (epicatechin gallate: ECG, epigallocatechin gallate: EGCG) and non-galloylated (catechin: C, epicatechin: EC, epigallocatechin: EGC) catechins, are considered to be the main contributors to the caries control potential of green tea. In this study, we intended to compare the antimicrobial effects of these representative green tea-derived catechins and their combined effects with fluoride on the acid production and aggregation of Streptococcus mutans. The effects of different catechins on the growth, aggregation and acid production of S. mutans, and the combined effect of catechins and potassium fluoride (2 mm at pH 7.0, 0.3 mm at pH 5.5) on S. mutans acid production were measured by anaerobic culture, turbidity changes due to aggregation, and pH-stat methods. Molecular docking simulations were also performed to investigate the interactions between catechins and membrane-embedded enzyme II complex (EIIC), a component of the phosphoenolpyruvate-dependent phosphotransferase system (sugar uptake-related enzyme). ECG or EGCG at 1 mg/mL significantly inhibited the growth of S. mutans, induced bacterial aggregation, and decreased glucose-induced acid production (p < 0.05). All catechins were able to bind to EIIC in silico, in the following order of affinity: EGCG, ECG, EGC, EC, and C. Furthermore, they enhanced the inhibitory effects of fluoride at pH 5.5 and significantly inhibited S. mutans acid production by 47.5–86.6% (p < 0.05). These results suggest that both galloylated and non-galloylated catechins exhibit antimicrobial activity, although the former type demonstrates stronger activity, and that the caries control effects of green tea may be due to the combined effects of multiple components, such as catechins and fluoride. The detailed mechanisms underlying these phenomena and the in vivo effect need to be explored further.
Human Epidermal Keratinocytes in Culture: A Story of Multiple Recipes for a Single Cell Type
Authors: Poumay Yves , Faway Emilie
Published: October 2023

Background: For one half-century, cultures of human epidermal keratinocytes have opened new paths of research in skin biology and dermatology. Either performed with serum and feeder layer, in serum-free conditions, or in autocrine conditions, cells cultured as monolayers became research materials for basic science and dermatology, as well as a source for grafting, particularly to treat severely burned patients. More recently, tissue reconstruction at air-liquid interface has opened new perspectives for in vitro toxicology, studies of epidermal barrier, and modeling skin diseases. Summary: This review presents a brief retrospective of the emergence of keratinocyte-based culture techniques. It also presents opportunities and eventual problems that researchers might encounter when exploring the skin using such procedures. Key Messages: While methodologies in tissue culture evolve, the multiplicity of procedures concomitantly increases, requiring to make some selective but difficult choice. Keeping tracks of technological evolution in epidermal cell culture should help choosing the adequate methodology for a specific investigation or innovating with new, more dedicated ones.
Relationship between the Ratio of Red Cell Distribution Width to Albumin and 28-Day Mortality among Chinese Patients over 80 Years with Atrial Fibrillation
Authors: Chen Conggai , Cai Jiasheng , Song Bin , Zhang Lingyun , Wang Wei , Luo Rong , Zhang Yi , Ling Yunhao , Wu Chuntao , Wang Zilong , Liu Haibo , Wu Yumei , Qu Xinkai
Published: October 2023

Introduction: Atrial fibrillation (AF) is a prevalent heart arrhythmia in elderly adults aged 80 years or older. The red cell distribution width (RDW) to albumin ratio has been acknowledged as a reliable prognostic marker for poor outcomes in a variety of disorders. However, there exists limited scientific evidence on the association of RDW to albumin (RAR) with mortality in geriatric individuals with AF. Methods: From January 2015 to June 2020, a retrospective study was conducted in a tertiary academic institution that diagnosed 1,141 elderly adults with AF. The RAR value was calculated as the ratio of RDW (%) to albumin (g/dL). The potential association between RAR and cardiovascular mortality and the risk of all-cause mortality within 28 days was evaluated by means of multivariable Cox regression analysis. Results: The 28-day all-cause and cardiovascular mortality rates were 8.7% and 3.3%, respectively. Increased RAR tertiles were found to be significantly associated with greater all-cause mortality (T1: 1.6%; T2: 6.2%; T3: 18.1%, p < 0.001) and cardiovascular mortality (T1: 0.8%; T2: 2.9%; T3: 6.3%, p < 0.001) using Kaplan-Meier analysis. Continuous RAR had a positive association with all-cause mortality (hazard ratios [HR] = 1.42, 95% confidence interval [CI] 1.23–1.65) and cardiovascular mortality (HR = 1.31, 95% CI: 1.05–1.64), even after accounting for numerous confounding variables. In comparison to the T1 group, individuals with the highest RAR levels displayed a greater risk of all-cause mortality (HR = 2.73, 95% CI: 1.11–6.74) and cardiovascular mortality (HR = 2.59, 95% CI: 0.69–9.78). Increased RAR levels were related to higher rates of cardiovascular and all-cause mortality across almost all subgroups. Conclusion: RAR is independently correlated with 28-day all-cause mortality and cardiovascular mortality in AF-affected individuals aged ≥80.
High Incidence of Appendiceal Neoplasms in the Elderly: A Critical Concern for Non-Surgical Treatment
Authors: Issin Gizem , Demir Fatih , Guvendir Bakkaloglu Irem , Cagatay Diren Vuslat , Aktug Simsek Hasan , Yilmaz Ismail , Zemheri Ebru
Published: October 2023

Objective: Appendiceal neoplasms (ANs) are rare tumors that are often discovered incidentally during histopathological examinations. The increasing incidence of ANs is a critical issue in the non-operative management of acute appendicitis. This study aimed to document the temporal trends over a 12-year period by analyzing the clinical presentation, imaging findings, and histopathological features of ANs. Subjects and Methods: Health records of patients who underwent appendectomy from 2011 to 2022 were examined. Demographic and clinical data, laboratory results, imaging findings, and histopathological features were documented. The characteristics of both ANs and non-neoplastic cases were evaluated. Results: A total of 22,304 cases were identified, of which 330 (1.5%) were diagnosed with ANs. The odds ratio for ANs increased with age, with the highest odds ratio observed in patients aged 70 or older. Receiver Operating Characteristic analysis showed that age and appendiceal diameter were significant predictors of ANs. An optimal age cut-off point of 28.5 years was determined, yielding a sensitivity of 72% and a specificity of 64%. For appendiceal diameter, the optimal cut-off was found to be 9.5 mm, exhibiting a sensitivity of 77% and a specificity of 56%. Conclusion: Although the incidence of ANs remains relatively low, a steady increase has been observed over the past decade. The increasing rate of ANs raises concerns regarding non-surgical management options. The results of this study highlight the importance of considering ANs as a potential diagnosis in older patients and in patients with an appendix diameter greater than 9.5 mm. These findings may have implications for treatment and management.
The performance of Naïve Bayes, support vector machine, and logistic regression on Indonesia immigration sentiment analysis
Authors: Assiroj Priati , Kurnia Asep , Alam Sirojul
Published: October 2023

In recent years various attempts have been made to automatically mine opinions and sentiments from natural language in online networking messages, news, and product review businesses. Sentiment analysis is needed as an effort to improve service performance in the organization. In this paper, we have explored the polarization of positive and negative sentiments using Twitter user reviews. Sentiment analysis is carried out using the Naïve Bayes (NB), support vector machine (SVM), and logistic regression (LR) model then compares the results of these three models. The results of the experiment showed that the accuracy of LR was better than SVM and NB, namely 77%, 76%, and 70%.
АНАЛІЗ ВИКОРИСТАННЯ МЕТОДІВ СУЧАСНОЇ МІКРОСКОПІЇ IN VIVO ДЛЯ ДІАГНОСТИКИ ТА ЛІКУВАННЯ ЗЛОЯКІСНИХ НОВОУТВОРЕНЬ
Authors: Крючина Є. А. , Крючин А. А.
Published: October 2023

Ендоскопічна оптична мікроскопія in vivo надає інструмент для оцінювання архітектури та морфології тканини, що подібні до стандартного гістологічного дослідження, без необхідності видалення тканини. У цій статті автори зосередились на технологіях оптичного зображення in vivo, що мають потужний потенціал для суттєвого покращення діагностики та терапії злоякісних пухлин, а саме флуоресцентної конфокальної мікроскопії, оптичної когерентної томографії, мікроскопії світлового листа, двофотонної та високороздільної мікроскопії, атомно-силової мікроскопії, електронної мікроскопії тощо. Досліджено технологічні принципи, доклінічні та клінічні дослідження, що аналізують чутливість та специфічність зазначених методів у діагностиці та лікуванні різних варіантів злоякісних новоутворень, методи комп'ютерного оброблення зображень, обговорено перспективи вдосконалення зазначених технологій, подальші перспективи для розроблення новітніх оптичних пристроїв для діагностики та лікування злоякісних пухлин.
ІІНФОРМАЦІЙНІ АСПЕКТИ КІЛЬКІСНОГО ОЦІНЮВАННЯ ПСИХІЧНОГО ЗДОРОВ'Я ІНДИВІДА
Authors: Мінцер О. П. , Новик А. М.
Published: October 2023

Оцінювання психічного здоров'я людини є, мабуть найважливішою та найскладнішою складовою визначення здоров'я індивіда та популяції. Проаналізовано концептуальну можливість кількісного оцінювання психічного здоров'я та визначення критерію психічного здоров'я індивіда та популяції. Висловлено думку, що на даний період розвитку медицини методика інтегрального оцінювання психічного здоров'я відсутня. Відповідно необхідна додаткова робота для вивчення факторів, пов'язаних із психічним здоров'ям і процесами прийняття рішень стосовно політики оцінювання та укріплення психічного здоров'я. Головне - створення інтегрального кількісного критерія оцінювання психічного здоров'я людини. Існує потреба у достовірних і надійних показниках стану психічного здоров'я індивіда та популяції, а також в обґрунтуванні показників для відстеження валідності та справедливості даних. Рівень електронних досліджень в області психічного здоров'я постійно зростає. Це пов'язане з надзвичайно швидким зростанням впровадження інформаційних технологій, що включають Інтернет речей, робототехніку, штучний інтелект, який застосовується для надання психіатричних послуг.
УПРАВЛІННЯ ЦИФРОВИМИ ДАНИМИ В ПАТОЛОГІЇ
Authors: Бабінцева Л.Ю.
Published: October 2023

В усіх сферах людської діяльності активно відбуваються процеси цифровізації. Проаналізовано управління цифровими даними в сучасній патології, як одного з інформаційних середовищ, заснованих на цифрових зображеннях препаратів. Показано, що великі обсяги даних патології, які генеруються в клінічній практиці та в ході наукових досліджень, роблять актуальним завдання підвищення якості управління ними. Визначено, що управління сучасними цифровими даними в патології являється технологією, яка спрямована на надання персоналізованої та цільової медичної допомоги в даний час і найближчому майбутньому. За результатами дослідження зроблено висновки про тенденції управління цифровими даними в патології, що пов'язані з розвитком програмного та апаратного забезпечення цифровізації, зокрема інструментів аналізу зображень, емуляцією діагностичних процедур, управлінням великими об'ємами зображень високої роздільної здатності, а також впровадженням штучного інтелекту.
ІНФОРМАЦІЙНЕ ОЦІНЮВАННЯ ЗНАЧЕННЯ СПІВВІДНОШЕННЯ О2/СО2 У ФІЗІОЛОГІЇ ДИХАННЯ
Authors: Мінцер О.П. , Щукін В. С.
Published: October 2023

У статті на основі аналізу відомих фактів про фізіологію дихання людини, пропонуються твердження про існування нової групи фізіологічних констант, пов'язаних із оцінюванням співвідношення О2/СО2 під час газообміну. Розгляд зазначеного співвідношення як важливої константи гомеостазу дозволяє зробити деякі висновки, що можуть мати практичне значення. Обговорення можливості визнання співвідношення О2/СО2 ~ 1 фізіологічною константою гомеостазу людського організму.
Передбачається висвітлити тему в трьох повідомленнях. У першому наведено факти фізіології дихання, аналізується значення та протиріччя дихального коефіцієнту, мертвого простору, розглядаються необхідні положення фізіології дихання. В другому повідомленні наводяться необхідні положення газоаналізу і, в третьому проаналізовано можливості виділення нових фізіологічних констант. Зроблено висновки за першим повідомленням. Між «взяттям до уваги (як нульова гіпотеза)» існування факту співвідношення О2/СО2 ~ 1 і визнанням його як константи гомеостазу існує велика дистанція, на якій «розташовуються» багато проміжних висновків, що логічно та обґрунтовано випливають із факту визнання існування нової фізіологічної константи. Розгляд застосування співвідношення рО2 ~ рСО2 може забезпечити новий підхід до повнішого розуміння ризику хронічних захворювань, стратегії поведінки для забезпечення здорового способу життя, зокрема, розумінню того, як людина має будувати склад своєї дієти (кількість жирів, вуглеводів або білків) для отримання необхідної енергії, а для спеціалістів - уявлення про фізіологію газообміну та особливості метаболізму, що раніше не вивчалися в епідеміології хронічних захворювань.
СИСТЕМНА БІОМЕДИЦИНА ЯК ОСНОВА ПЕРСОНАЛІЗОВАНОЇ ТА ПРЕЦИЗІЙНОЇ МЕДИЦИНИ
Authors: Мінцер О.П. , Бабінцева Л.Ю. , Мохначов С.І. , Суханова О.О.
Published: October 2023

Розглянуто питання визначення ролі системної біомедицини в досягненні мети персоналізованої медицини. Зауважено, що використання принципів і методів системної біомедицини надає нові можливості у вивченні хронічних багатофакторних захворювань людини. Сучасні розробки в області машинного навчання (з акцентом на глибинне навчання) можуть дозволити в майбутньому виконувати процес персоналізованої діагностики ранніх порушень метаболізму в умовах клініки. Необхідне вирішення питань ідентифікації вибору рішення в персоналізованій медицині, класифікації ризиків подібної стратегії, математичних методів зіставлення можливих підходів.
Short‐Term Ambient Air Pollution Exposure and Risk of Out‐of‐Hospital Cardiac Arrest in Sweden: A Nationwide Case‐Crossover Study
Authors: Dahlquist Marcus , Frykman Viveka , Hollenberg Jacob , Jonsson Martin , Stafoggia Massimo , Wellenius Gregory A. , Ljungman Petter L. S.
Published: October 2023

Background

Air pollution is one of the main risk factors for cardiovascular disease globally, but its association with out‐of‐hospital cardiac arrest at low air pollution levels is unclear. This nationwide study in Sweden aims to investigate if air pollution is associated with a higher risk of out‐of‐hospital cardiac arrest in an area with relatively low air pollution levels.

Methods and Results

This study was a nationwide time‐stratified case‐crossover study investigating the association between short‐term air pollution exposures and out‐of‐hospital cardiac arrest using data from the SRCR (Swedish Registry for Cardiopulmonary Resuscitation) between 2009 and 2019. Daily air pollution levels were estimated in 1×1‐km grids for all of Sweden using a satellite‐based machine learning model. The association between daily air pollutant levels and out‐of‐hospital cardiac arrest was quantified using conditional logistic regression adjusted for daily air temperature. Particulate matter <2.5 μm exposure was associated with a higher risk of out‐of‐hospital cardiac arrest among a total of 29 604 cases. In a multipollutant model, the association was most pronounced for intermediate daily lags, with an increased relative risk of 6.2% (95% CI, 1.0–11.8) per 10 μg/m
3
increase of particulate matter <2.5 μm 4 days before the event. A similar pattern of association was observed for particulate matter <10 μm. No clear association was observed for O
3
and NO
2
.

Conclusions

Short‐term exposure to air pollution was associated with higher risk of out‐of‐hospital cardiac arrest. The findings add to the evidence of an adverse effect of particulate matter on out‐of‐hospital cardiac arrest, even at very low levels below current regulatory standards.
An Experimental Analysis of the Prize-Probability Tradeoff in Stopping Problems
Authors: Antler Yair , Arad Ayala
Published: October 2023

We experimentally examine how individuals commit to a cutoff stopping rule when facing a sequence of independent lotteries. We identify two main behavior patterns: (1) a small share of participants consistently choose stopping rules whose gain bound (i.e., the accumulated gain at which the sequence stops) is larger than the loss bound, and (2) a larger share of participants consistently choose rules whose loss bound is larger than the gain bound. We introduce a procedural choice model that accounts for these patterns and show that the behavior of most of our participants is inconsistent with prominent theories of decision under risk.
Inaccurate Statistical Discrimination: An Identification Problem
Authors: Bohren J. Aislinn , Haggag Kareem , Imas Alex , Pope Devin G.
Published: October 2023

We study inaccurate beliefs as a source of discrimination. Economists typically characterize discrimination as stemming from a taste-based (preference) or accurate statistical (belief-based) source. While individuals may have inaccurate beliefs about how relevant characteristics (e.g., productivity, signals) are correlated with group identity, fewer than 7% of empirical discrimination papers in economics consider the possibility of such inaccurate statistical discrimination. Using theory and a labor market experiment, we show that failing to account for inaccurate beliefs leads to a misclassification of source. We outline three methods to identify source: varying observed signals, belief elicitation, and an intervention to target inaccurate beliefs.
Kefeli Mescidi in Istanbul
Authors: Varsallona Jessica
Published: October 2023

This article offers a brief analysis of the architectural features of the building Kefeli Mescidi in Istanbul and supports its identification as a Byzantine monastic dining hall. The analysis of Late Byzantine written sources in connection to the topographical and material data of the building supports the association with the famous Constantinopolitan monastery of St John of Petra and its refectory.
Beyond the Dār al-Islām/Dār al-ḥarb Paradigm
Authors: Rizzo Alessandro
Published: October 2023

For a long time, scholarship concerning the relations between the Mamluks and Christian powers has been heavily influenced by the traditional dichotomy between dār al-Islām and dār al-ḥarb. This paradigm has often led historians to misinterpret the nature of the diplomatic documents issued by the chancery in Cairo.

Taking into account new perspectives on the dialogue between Muslim and non-Muslim powers, the article examines the principles underlying the diplomatic dialogue in wartime and in peacetime through the lens of Mamluk diplomatic sources. Through this analysis, the paper illustrates how the discipline of Diplomatics can offer a direct approach to reconsidering some historiographical narratives and to understanding the real nature of diplomatic exchange and its symbolic representation.