bluuebunny/crossref_metadata_2025 huggingface dataset:
Dementia, Substance Misuse, and Social Determinants of Health: American Indian and Alaska Native Peoples’ Prevention, Service, and Care
Authors: Crouch Maria C. , Cheromiah Salazar Maredyth B. R. , Harris Steven J. , Rosich Rosellen M.
Published: January 2023

Background

American Indian and Alaska Native (AI/AN) peoples are disproportionately impacted by substance use disorders (SUDs) and health consequences in contrast to all racial/ethnic groups in the United States. This is alarming that AI/AN peoples experience significant health disparities and disease burden that are exacerbated by settler-colonial traumas expressed through prejudice, stigma, discrimination, and systemic and structural inequities. One such compounding disease for AI/AN peoples that is expected to increase but little is known is Alzheimer's disease and related dementias (ADRD). AI/AN approaches for understanding and treating disease have long been rooted in culture, context, and worldview. Thus, culturally based prevention, service, and caregiving are critical to optimal outcomes, and investigating cultural beliefs regarding ADRD can provide insights into linkages of chronic stressors, disease, prevention and treatment, and the role of substance misuse.

Method

To understand the cultural practices and values that compose AI/AN Elder beliefs and perceptions of ADRD, a grounded theory, qualitative study was conducted. Twelve semistructured interviews with AI/AN Elders (M age = 73; female = 8, male = 4) assessed the etiology, course, treatment, caregiving, and the culturally derived meanings of ADRD, which provides a frame of understanding social determinants of health (SDH; eg, healthcare equity, community context) and impacts (eg, historical trauma, substance misuse) across the lifespan.

Results

Qualitative analyses specific to disease etiology, barriers to treatment, and SDH revealed 6 interrelated and nested subthemes elucidating both the resilience and the chronic stressors and barriers faced by AI/AN peoples that directly impact prevention, disease progression, and related services: (1) postcolonial distress; (2) substance misuse; (3) distrust of Western medicine; (4) structural inequities; (5) walking in two worlds; and (6) decolonizing and indigenizing medicine.

Conclusion

Barriers to optimal wellbeing and SDH for AI/AN peoples are understood through SUDs, ADRD, and compounding symptoms upheld by colonial traumas and postcolonial distress. En masse historical and contemporary discrimination and stress, particularly within Western medicine, both contextualizes the present and points to the ways in which the strengths, wisdom, and balance inherent in AI/AN culture are imperative to the holistic health and healing of AI/AN peoples, families, and communities.
Surveillance Intervals for Barrett’s Esophagus Need to be Changed-Surveillance Intervals are Too Long and Should be Shortened
Authors: Haddad James D. , Sawas Tarek
Published: January 2023

Barrett’s esophagus (BE) surveillance remains fraught with controversy and variation in real-world clinical practices. The application of current guideline-recommended surveillance intervals has not significantly impacted the incidence of esophageal adenocarcinoma (EAC), nor survival. One fifth of patients with EAC present in the first year after a negative upper endoscopy. Additionally, the progression from BE to EAC may occur in a non-linear fashion and more rapidly than previously believed due sudden genomic catastrophes requiring intensified surveillance. Emerging data supports the role of molecular markers for risk stratification and a more patient-centered surveillance approach rather than less vigorous universal surveillance intervals.
Formyl peptide receptor 2 activation by mitochondrial formyl peptides stimulates the neutrophil proinflammatory response via the ERK pathway and exacerbates ischemia–reperfusion injury
Authors: Cao Yirui , Chen Juntao , Liu Feng , Qi Guisheng , Zhao Yufeng , Xu Shihao , Wang Jiyan , Zhu Tongyu , Zhang Yi , Jia Yichen
Published: January 2023

Background

Ischemia–reperfusion injury (IRI) is an inevitable process in renal transplantation that significantly increases the risk of delayed graft function, acute rejection, and even graft loss. Formyl peptide receptor 2 (FPR2) is an important receptor in multiple septic and aseptic injuries, but its functions in kidney IRI are still unclear. This study was designed to reveal the pathological role of FPR2 in kidney IRI and its functional mechanisms.

Methods

To explore the mechanism of FPR2 in kidney IRI, the model rats were sacrificed after IRI surgery. Immunofluorescence, enzyme-linked immunosorbent assays, and western blotting were used to detect differences in the expression of FPR2 and its ligands between the IRI and control groups. WRW4 (WRWWWW-NH2), a specific antagonist of FPR2, was administered to kidney IRI rats. Kidney function and pathological damage were detected to assess kidney injury and recovery. Flow cytometry was used to quantitatively compare neutrophil infiltration among the experimental groups. Mitochondrial formyl peptides (mtFPs) were synthesized and administered to primary rat neutrophils together with the specific FPR family antagonist WRW4 to verify our hypothesis in vitro. Western blotting and cell function assays were used to examine the functions and signaling pathways that FPR2 mediates in neutrophils.

Results

FPR2 was activated mainly by mtFPs during the acute phase of IRI, mediating neutrophil migration and reactive oxygen species production in the rat kidney through the ERK1/2 pathway. FPR2 blockade in the early phase protected rat kidneys from IRI.

Conclusions

mtFPs activated FPR2 during the acute phase of IRI and mediated rat kidney injury by activating the migration and reactive oxygen species generation of neutrophils through the ERK1/2 pathway.
DNA methylome and transcriptome identified Key genes and pathways involved in Speckled Eggshell formation in aged laying hens
Authors: Cheng Xue , Li Xinghua , Liu Yuchen , Ma Ying , Zhang Ruiqi , Zhang Yalan , Fan Cuidie , Qu Lujiang , Ning Zhonghua
Published: January 2023

Background

The quality of poultry eggshells is closely related to the profitability of egg production. Eggshell speckles reflect an important quality trait that influences egg appearance and customer preference. However, the mechanism of speckle formation remains poorly understood. In this study, we systematically compared serum immune and antioxidant indices of hens laying speckled and normal eggs. Transcriptome and methylome analyses were used to elucidate the mechanism of eggshell speckle formation.

Results

The results showed that seven differentially expressed genes (DEGs) were identified between the normal and speckle groups. Gene set enrichment analysis (GSEA) revealed that the expressed genes were mainly enriched in the calcium signaling pathway, focal adhesion, and MAPK signaling pathway. Additionally, 282 differentially methylated genes (DMGs) were detected, of which 15 genes were associated with aging, including ARNTL, CAV1, and GCLC. Pathway analysis showed that the DMGs were associated with T cell-mediated immunity, response to oxidative stress, and cellular response to DNA damage stimulus. Integrative analysis of transcriptome and DNA methylation data identified BFSP2 as the only overlapping gene, which was expressed at low levels and hypomethylated in the speckle group.

Conclusions

Overall, these results indicate that aging- and immune-related genes and pathways play a crucial role in the formation of speckled eggshells, providing useful information for improving eggshell quality.
Genome-wide identification and molecular characterization of the AP2/ERF superfamily members in sand pear (Pyrus pyrifolia)
Authors: Xu Yue , Li Xiaona , Yang Xiong , Wassie Misganaw , Shi Haiyan
Published: January 2023

Background

‘Whangkeumbae’ (Pyrus pyrifolia) is a typical climacteric fruit variety of sand pear with excellent taste. However, the rapid postharvest ethylene production limits the shelf life of ‘Whangkeumbae’ fruit. AP2/ERF superfamily is a large family of transcription factors involved in plant growth and development, including fruit ripening and senescence through the ethylene signaling pathway. The numbers and functions of AP2/ERF superfamily members in sand pear remain largely unknown.

Results

In this study, a total of 234 AP2/ERF family members were identified through the transcriptome of Pyrus pyrifolia ‘Whangkeumbae’ (17 genes) and Pyrus pyrifolia genome (223 genes) analyses. Six genes (Accession: EVM0023062.1, EVM0034833.1, EVM0027049.1, EVM0034047.1, EVM0028755.1, EVM0015862.1) identified via genome analysis shared 100% identity with PpERF14-L, PpERF5-L, PpERF3a, PpERF3, PpERF017 and PpERF098, respectively, which were identified from transcriptome sequencing. Further, the AP2/ERF superfamily members were divided into AP2, ERF, and RAV subfamilies, each comprising 38, 188, and 8 members, respectively. Tissue-specific expression analysis showed that PpERF061, PpERF113, PpERF51L-B, PpERF5-L, and PpERF017 were predominantly expressed in fruits than in other tissues. Additionally, PpERF5-L and PpERF017 showed higher expressions at the early stage of fruit development. While, PpERF51B-L exhibited higher expression during the fruit ripening stage. Besides, PpERF061 and PpERF113 had pronounced expressions during fruit senescence.

Conclusion

These results indicate that PpERF061, PpERF113, PpERF51L-B, PpERF5-L, and PpERF017 could play crucial roles in sand pear fruit development, ripening, and senescence. Overall, this study provides valuable information for further functional analysis of the AP2/ERF genes during fruit ripening and senescence in sand pear.
Deciphering key genomic regions controlling flag leaf size in wheat via integration of meta-QTL and in silico transcriptome assessment
Authors: Kong Binxue , Ma Jingfu , Zhang Peipei , Chen Tao , Liu Yuan , Che Zhuo , Shahinnia Fahimeh , Yang Delong
Published: January 2023

Background

Grain yield is a complex and polygenic trait influenced by the photosynthetic source-sink relationship in wheat. The top three leaves, especially the flag leaf, are considered the major sources of photo-assimilates accumulated in the grain. Determination of significant genomic regions and candidate genes affecting flag leaf size can be used in breeding for grain yield improvement.

Results

With the final purpose of understanding key genomic regions for flag leaf size, a meta-analysis of 521 initial quantitative trait loci (QTLs) from 31 independent QTL mapping studies over the past decades was performed, where 333 loci eventually were refined into 64 meta-QTLs (MQTLs). The average confidence interval (CI) of these MQTLs was 5.28 times less than that of the initial QTLs. Thirty-three MQTLs overlapped the marker trait associations (MTAs) previously reported in genome-wide association studies (GWAS) for flag leaf traits in wheat. A total of 2262 candidate genes for flag leaf size, which were involved in the peroxisome, basal transcription factor, and tyrosine metabolism pathways were identified in MQTL regions by the in silico transcriptome assessment. Of these, the expression analysis of the available genes revealed that 134 genes with > 2 transcripts per million (TPM) were highly and specifically expressed in the leaf. These candidate genes could be critical to affect flag leaf size in wheat.

Conclusions

The findings will make further insight into the genetic determinants of flag leaf size and provide some reliable MQTLs and putative candidate genes for the genetic improvement of flag leaf size in wheat.
Antimicrobial activity of D-amino acid in combination with photo-sonoactivated hypericin nanoparticles against Acinetobacter baumannii
Authors: Pourhajibagher Maryam , Hosseini Nava , Bahador Abbas
Published: January 2023

Background

The emergence of multidrug-resistant Acinetobacter baumannii strains is increasing worldwide. To overcome these life-threatening infections, the development of new treatment approaches is critical. For this purpose, this study was conducted to determine the antimicrobial photo-sonodynamic therapy (aPSDT) using hypericin nanoparticles (HypNP) in combination with D-Tryptophan (D-Trp) against A. baumannii.

Materials and methods

HypNP was synthesized and characterized, followed by the determination of the fractional inhibitory concentration (FIC) index of HypNP and D-Trp by checkerboard assay. Next, the antimicrobial and anti-biofilm potential of HypNP@D-Trp-mediated aPSDT against A. baumannii was evaluated. Finally, the anti-virulence activity of aPSDT using HypNP@D-Trp was accessed following the characterization of HypNP@D-Trp interaction with AbaI using in silico virtual screening and molecular docking.

Results

A synergistic activity in the combination of HypNP and D-Trp against A. baumannii was observed with a FIC index value of 0.5. There was a 5.10 log10 CFU/mL reduction in the cell viability of A. baumannii when the bacterial cells were treated with 1/2 × MIC of HypNP@D-Trp and subsequently exposed to ultrasound waves and blue light (P < 0.05). Moreover, a significant biofilm degradation effect on biofilm-associated cells of A. baumannii was observed after treatment with aPSDT using 2 × MIC of HypNP@D-Trp in comparison with the control groups (P < 0.05). According to the molecular docking analysis of the protein-ligand complex, Hyp with a high affinity for AbaI showed a binding affinity of − 9.41 kcal/mol. Also, the expression level of abaI gene was significantly downregulated by 10.32-fold in A. baumannii treated with aPSDT as comprised with the control group (P < 0.05).

Conclusions

It can be concluded that HypNP@D-Trp-mediated aPSDT can be considered a promising strategy to overcome the infections caused by A. baumannii by reducing the growth of bacterial biofilm and decreasing the expression of abaI as a gene involved in A. baumannii biofilm formation.
Clinical characteristics and risk factors of organ failure and death in necrotizing pancreatitis
Authors: Yu Liqing , Xie Fengwen , Luo Lingyu , Lei Yupeng , Huang Xin , Yang Xiaoyu , Zhu Yong , He Cong , Li Nianshuang , He Wenhua , Zhu Yin , Lu Nonghua , Yu Bingjun
Published: January 2023

Background

Organ failure (OF) and death are considered the most significant adverse outcomes in necrotizing pancreatitis (NP). However, there are few NP-related studies describing the clinical traits of OF and aggravated outcomes.

Purpose

An improved insight into the details of OF and death will be helpful to the management of NP. Thus, in our research, we addressed the risk factors of OF and death in NP patients.

Methods

We performed a study of 432 NP patients from May 2017 to December 2021. All patients with NP were followed up for 36 months. The primary end-points were risk factors of OF and death in NP patients. The risk factors were evaluated by logistic regression analysis.

Results

NP patients with OF or death patients were generally older, had a higher APACHE II score, longer hospital stay, longer ICU stay, as well as a higher incidence of severe acute pancreatitis (SAP), shock and pancreatic necrosis. Independent risk factors related to OF included BMI, APACHE II score and SAP (P < 0.05). Age, shock and APACHE II score (P < 0.05) were the most significant factors correlated with the risk of death in NP patients. Notably, increased mortality was linked to the number of failed organs.

Conclusions

NP is a potentially fatal disease with a long hospital or ICU stay. Our study indicated that the incidence of OF and death in NP patients was 69.9% and 10.2%, respectively. BMI, SAP, APACHE II score, age and shock are potential risk factors of OF and death in NP patients. Clinicians should focus on these factors for early diagnosis and appropriate therapy.
IgG4-related eosinophilic pleural effusion: a case report
Authors: Wang Lina , Di Jiting , Huang Junfang , Guo Cuiyan
Published: January 2023

Background

The diagnosis of unilateral eosinophilic pleural effusion (EPE) is difficult, especially for the elderly. IgG4-related disease (IgG4-RD) is a rare cause of EPE.

Case presentation

An 81-year-old man was admitted to the hospital for dyspnea due to right pleural effusion. Laboratory examination shows elevated IgG4 and eosinophils in both serum and pleural fluid. The patient was diagnosed with IgG4-RD by video-assisted thoracoscopy and pleural biopsy. We found no evidence of other organ involvement except for the EPE and history of prurigo. He was treated with prednisolone 40 mg daily orally and pleural effusion decreased significantly.

Conclusion

IgG4-RD should be considered in the differential diagnosis of EPE in the elderly. High effusion IgG4 concentration may be an indication of IgG4-related pleural lesions.
Prevention of mother-to-child transmission of HIV in Kermanshah, west of Iran from 2014 to 2021
Authors: Lorestani Roya Chegene , Rostamian Mosayeb , Akya Alisha , Rezaeian Shahab , Afsharian Mandana , Habibi Reza , Bozorgomid Arezoo , Kazemisafa Narges , Jafari Somayeh , Yeilaghi Soliman , Salehi Mansour Mohammad , Namdari Hiva , Ghadiri Keyghobad
Published: January 2023

Background

This study aimed to evaluate the implementation of the prevention of mother-to-child transmission (PMTCT) of the HIV-PMTCT program in Kermanshah, west of Iran, from 2014 to 2021.

Methods

The data of all HIV-infected mothers and their infants who were monitored by the Kermanshah behavioral diseases counseling center was extracted and recorded in a checklist.

Results

Out of 95 included infant, 45 (47.4%) were girls and 50 (52.6%) were boys. The mothers were mostly infected with HIV via their infected spouse. The pregnancies of 77 cases (82.1%) were in accordance with the national guideline. The average length of treatment for this group was 185 days. Of the 18 mothers who did not receive treatment, nine were diagnosed during childbirth and nine had no available information. All infants born from infected mothers underwent after-birth-antiretroviral prophylaxis, and all remained healthy. There was no statistically significant relationship between the birth weight and height of neonates with maternal age, maternal last viral load, disease stage, education, and maternal CD4 levels. Only a statistically significant relationship was observed between the duration of treatment and the infants’ weight.

Conclusion

The results suggest the feasibility and effectiveness of the PMTCT program for HIV-positive mothers in Kermanshah. It seems that if pregnant HIV-positive women are diagnosed early and covered by a good prevention program on time, the risk of HIV to their babies will be reduced, significantly.
Use of the Strengths and Difficulties Questionnaire in child and school health services among children aged 4 and 6 years in Southern Norway: clinical considerations
Authors: Mølland Eirin , Haraldstad Kristin , Abildsnes Eirik , Håland Åshild Tellefsen , Köpp Unni Mette Stamnes , Fegran Liv , Westergren Thomas
Published: January 2023

Background

Parent reported mental health can be assessed by the Strengths and Difficulties Questionnaire (SDQ). Currently, Norwegian norms for parent-reported SDQ do not exist, whereas Swedish, Danish, and United Kingdom (UK) norms have been published. We aimed to (1) describe parent-reported SDQ among children aged 4 and 6 years in Southern Norway, (2) evaluate empirical cutoff values within the context of the Starting RightTMproject in relation to the Swedish, Danish, and UK cutoffs, and (3) evaluate the representativeness of the study sample with regard to parental socioeconomic status.

Methods

This study included parent-reported observations for 665 children (63% consent rate). Means and standard deviations were calculated for the domains of SDQ, and gender differences were assessed. Based on the Swedish, Danish, and UK cutoffs and the 80thand 90thpercentile cutoff values within the study, we calculated the total number of children with borderline and abnormal scores.

Results

Boys had higher mean total difficulties (7.3 vs 5.6) and impact scores (0.3 vs 0.1) and lower prosocial scores (8.3 vs 8.8) than girls. The differences in means were largest in the case of externalizing symptoms (5.0 vs 3.6) and hyperactivity subscore (3.2 vs 2.3). Using the UK cutoff values, 28 and 25 children had borderline and abnormal total difficulties scores, respectively. The corresponding numbers using the within study or Scandinavian cutoff values were 84–99 and 54–79, respectively. Overall, our study sample was well representative of the target population.

Conclusions

Our findings consistently indicated that girls had better SDQ scores than boys among children aged 4 and 6 years. Fewer children would be identified as having mental health difficulties using the UK cutoff values than using the Scandinavian age- and gender-relevant cutoff values.
Efficacy of three sputum specimens for the diagnosis of Mycobacterium avium complex pulmonary disease
Authors: Urabe Naohisa , Sakamoto Susumu , Masuoka Marie , Kato Chiaki , Yamaguchi Asuka , Tokita Nozomi , Homma Sakae , Kishi Kazuma
Published: January 2023

Background

In Mycobacterium avium complex pulmonary disease (MAC-PD), diagnosis requires a positive culture from at least two separate expectorated sputum specimens. The optimal number of sputum examinations remains unclear.

Objective

This study sought to elucidate the diagnostic yield of acid-fast bacilli in MAC-PD using 3 sputum specimens and to clarify the clinical characteristics of patients with MAC-PD diagnosed using 3 sputum specimens. Furthermore, we investigated the correlation between increased number of sputum specimens and diagnostic yield.

Methods

We reviewed the medical records of 139 patients with MAC-PD diagnosed at Toho University Omori Medical Center for whom at least three sputum specimens were examined before treatment from November 2014 through June 2021. Patients were classified into the 3-sputum diagnosed and the non-3 sputum diagnosed groups based on diagnostic procedure; clinical and radiological characteristics were compared. We also assessed diagnostic yield with the increased number of sputum specimens.

Results

Diagnostic yield with 3 sputum specimens was 16.5% (23/139). The 3-sputum diagnosed group had a lower body mass index [18.6(17–19.5) vs. 19.5(18–21.5); p = 0.014], and higher chest CT score [9(6.5–13) vs. 6(4–9); p = 0.011] including cavitary lesions (39.1% vs. 19%; p = 0.037) compared with the non-3 sputum diagnosed group. When the number of sputum specimens was increased to 6, the diagnostic yield increased to 23.7% (33/139).

Conclusion

Diagnostic yield with 3 sputum specimens was 16.5%. Patients diagnosed using 3 sputum specimens had more severe chest CT findings including cavitary lesions. Increasing the number of sputum specimens to 6 improved diagnostic yield by 7.2%.
The classification of flash visual evoked potential based on deep learning
Authors: Liang Na , Wang Chengliang , Li Shiying , Xie Xin , Lin Jun , Zhong Wen
Published: January 2023

Background

Visual electrophysiology is an objective visual function examination widely used in clinical work and medical identification that can objectively evaluate visual function and locate lesions according to waveform changes. However, in visual electrophysiological examinations, the flash visual evoked potential (FVEP) varies greatly among individuals, resulting in different waveforms in different normal subjects. Moreover, most of the FVEP wave labelling is performed automatically by a machine, and manually corrected by professional clinical technicians. These labels may have biases due to the individual variations in subjects, incomplete clinical examination data, different professional skills, personal habits and other factors. Through the retrospective study of big data, an artificial intelligence algorithm is used to maintain high generalization abilities in complex situations and improve the accuracy of prescreening.

Methods

A novel multi-input neural network based on convolution and confidence branching (MCAC-Net) for retinitis pigmentosa RP recognition and out-of-distribution detection is proposed. The MCAC-Net with global and local feature extraction is designed for the FVEP signal that has different local and global information, and a confidence branch is added for out-of-distribution sample detection. For the proposed manual features,a new input layer is added.

Results

The model is verified by a clinically collected FVEP dataset, and an accuracy of 90.7% is achieved in the classification task and 93.3% in the out-of-distribution detection task.

Conclusion

We built a deep learning-based FVEP classification algorithm that promises to be an excellent tool for screening RP diseases by using FVEP signals.
Evaluation the efficacy of oral immunization of broiler chickens with a recombinant Lactobacillus casei vaccine vector expressing the Carboxy-terminal fragment of α-toxin from Clostridium perfringens
Authors: Shamshirgaran Mohammad Ali , Golchin Mehdi , Salehi Mahmoud , Kheirandish Reza
Published: January 2023

Background

Clostridium perfringens (C. perfringens) is a serious anaerobic enteric pathogen causing necrotic enteritis (NE) in broiler chickens. Following the ban on antibiotics as growth promoters in animal feedstuffs, there has been a remarkable rise in occurrence of NE which resulted in considering alternative approaches, particularly vaccination. The objective of this work was to evaluate the recombinant Lactobacillus casei (L. casei) expressing the C-terminal domain of α-toxin from C. perfringens as a potential probiotic-based vaccine candidate to immunize the broiler chickens against NE.

Results

The broiler chickens immunized orally with recombinant vaccine strain were significantly protected against experimental NE challenge, and developed specific serum anti-α antibodies. Additionally, the immunized birds showed higher body weight gains compared with control groups during the challenge experiment.

Conclusions

The current study showed that oral immunization of broiler chickens with a safe probiotic-based vector vaccine expressing α-toxin from C. perfringens could provide protective immunity against NE in birds.
Accumulated hypertension burden on atrial fibrillation risk in diabetes mellitus: a nationwide population study
Authors: Choi JungMin , Lee So‑Ryoung , Choi Eue‑Keun , Lee HuiJin , Han MinJu , Ahn Hyo-Jeong , Kwon Soonil , Lee Seung-Woo , Han Kyung‑Do , Oh Seil , Lip Gregory Y. H.
Published: January 2023

Background

Patients with diabetes mellitus have an increased risk of incident atrial fibrillation (AF). The effect of accumulated hypertension burden is a less well-known modifiable risk factor. We explored the relationship between accumulated hypertension burden and incident AF in these patients.

Methods

We evaluated data for 526,384 patients with diabetes who underwent three consecutive health examinations, between 2009 and 2012, from the Korean National Health Insurance Service. Hypertension burden was calculated by assigning points to each stage of hypertension in each health examination: 1 for stage 1 hypertension (systolic blood pressure [SBP] 130–139 mmHg; diastolic blood pressure [DBP] 80–89 mmHg); 2 for stage 2 (SBP 140–159 mmHg and DBP 90–99 mmHg); and 3 for stage 3 (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg). Patients were categorized into 10 hypertensive burden groups (0–9). Groups 1–9 were then clustered into 1–3, 4–6, and 7–9.

Results

During a mean follow-up duration of 6.7 ± 1.7 years, AF was newly diagnosed in 18,561 (3.5%) patients. Compared to patients with hypertension burden 0, those with burden 1 to 9 showed a progressively increasing risk of incident AF: 6%, 11%, 16%, 24%, 28%, 41%, 46%, 57%, and 67% respectively. Clusters 1–3, 4–6, and 7–9 showed increased risks by 10%, 26%, and 45%, respectively, when compared to a hypertension burden of 0.

Conclusions

Accumulated hypertension burden was associated with an increased risk of incident AF in patients with diabetes. Strict BP control should be emphasized for these patients.
The effect of physician density on colorectal cancer stage at diagnosis: causal inference methods for spatial data applied on regional-level data
Authors: Draganic Dajana , Wangen Knut Reidar
Published: January 2023

Background

The early detection of colorectal cancer (CRC) through regular screening decreases its incidence and mortality rates and improves survival rates. Norway has an extremely high percentage of CRC cases diagnosed at late stages, with large variations across municipalities and hospital catchment areas. This study examined whether the availability of physicians related to CRC primary diagnosis and preoperative investigations, or physician density, contributes to the observed geographical differences in late-stage incidence rates.

Method

Municipality-level data on CRC stage at diagnosis were obtained from the Cancer Registry of Norway for the period 2012–2020. Physician density was calculated as the number of physicians related to CRC investigations, general practitioners (GPs) and specialists per 10,000 people, using physician counts per municipality and hospital areas from Statistics Norway. The relationship was examined using a novel causal inference method for spatial data—neighbourhood adjustment method via spatial smoothing (NA approach)—which allowed for studying the region-level effect of physician supply on CRC outcome by using spatially referenced data and still providing causal relationships.

Results

According to the NA approach, an increase in one general practitioner per 10,000 people will result in a 3.6% (CI −0.064 to −0.008) decrease in late-stage CRC rates. For specialists, there was no evidence of a significant correlation with late-stage CRC distribution, while for both groups, GPs and specialists combined, an increase of 1 physician per 10,000 people would be equal to an average decrease in late-stage incidence rates by 2.79% (CI −0.055 to −0.001).

Conclusion

The study confirmed previous findings that an increase in GP supply will significantly improve CRC outcomes. In contrast to previous research, this study identified the importance of accessibility to both groups of physicians—GPs and specialists. If GPs encounter insufficient workforces in hospitals and long delays in colonoscopy scheduling, they will less often recommend colonoscopy examinations to patients. This study also highlighted the efficiency of the novel methodology for spatially referenced data, which allowed us to study the effect of physician density on cancer outcomes within a causal inference framework.
Progranulin (PGRN) as a regulator of inflammation and a critical factor in the immunopathogenesis of cardiovascular diseases
Authors: Saeedi-Boroujeni Ali , Purrahman Daryush , Shojaeian Ali , Poniatowski Łukasz A. , Rafiee Fatemeh , Mahmoudian-Sani Mohammad-Reza
Published: January 2023

Immune dysregulation has been identified as a critical cause of the most common types of cardiovascular diseases (CVDs). Notably, the innate and adaptive immune responses under physiological conditions are typically regulated with high sensitivity to avoid the exacerbation of inflammation, but any dysregulation can probably be associated with CVDs. In this respect, progranulin (PGRN) serves as one of the main components of the regulation of inflammatory processes, which significantly contributes to the immunopathogenesis of such disorders. PGRN has been introduced among the secreted growth factors as one related to wound healing, inflammation, and human embryonic development, as well as a wide variety of autoimmune diseases. The relationship between the serum PGRN and TNF-α ratio with the spontaneous bacterial peritonitis constitute one of the independent predictors of these conditions. The full-length PGRN can thus effectively reduce the calcification of valve interstitial cells, and the granulin precursor (GRN), among the degradation products of PGRN, can be beneficial. Moreover, it was observed that, PGRN protects the heart against ischemia-reperfusion injury. Above all, PGRN also provides protection in the initial phase following myocardial ischemia-reperfusion injury. The protective impact of PGRN on this may be associated with the early activation of the PI3K/Akt signaling pathway. PGRN also acts as a protective factor in hyperhomocysteinemia, probably by down-regulating the wingless-related integration site Wnt/β-catenin signaling pathway. Many studies have further demonstrated that SARS-CoV-2 (COVID-19) has dramatically increased the risks of CVDs due to inflammation, so PGRN has drawn much more attention among scholars. Lysosomes play a pivotal role in the inflammation process, and PGRN is one of the key regulators in their functioning, which contributes to the immunomodulatory mechanism in the pathogenesis of CVDs. Therefore, investigation of PGRN actions can help find new prospects in the treatment of CVDs. This review aims to summarize the role of PGRN in the immunopathogenesis of CVD, with an emphasis on its treatment.
Factors affecting the quality of life after ischemic stroke in young adults: a scoping review
Authors: Gurková Elena , Štureková Lenka , Mandysová Petra , Šaňák Daniel
Published: January 2023

Purpose

To synthesize the body of knowledge on the factors influencing the quality of life (QoL) after ischemic stroke (IS) in young adults.

Methods

Guidelines regarding the scoping review methodology developed by the Joanna Briggs Institute, and the PRISMA-ScR checklist for a scoping review was used in this paper. A total of 1197 studies were identified through a bibliographic search in Web of Science, MEDLINE, PsycInfo, ScienceDirect, Scopus, and ProQuest Science Database. Articles published between the years 2000–2021 were included.

Results

A total of nine papers were finally selected to respond to the research question. Three studies were prospective longitudinal studies compared QoL between young stroke and age-matched controls from the general population. Across all the analysed studies, 14 variables potentially associated with QoL were identified. QoL in young patients is mainly affected by clinical outcomes after IS (scored by the modified Rankin scale and the Barthel index—favourable initial functional status and higher independence in ADL leads to higher QoL) and psychological factors (post-stroke fatigue and depression—higher levels of fatigue and depression lead to lower QoL). The reviewed studies emphasized the importance of functional outcomes, post-stroke depression, fatigue and anxiety and early return to work.

Conclusion

Further longitudinal studies are needed to identify the trajectory of post-stroke psychosocial symptoms over time and other potential predictors of unfavourable long-term QoL, thus specific young stroke rehabilitation and stroke self-management support programmes should be developed (address physical, psychological factors which influence the psychosocial adaptation post-stroke and the perception of the QoL).
Sequestration of Gβγ by deubiquitinated arrestins into the nucleus as a novel desensitization mechanism of G protein–coupled receptors
Authors: Min Xiao , Sun Ningning , Wang Shujie , Zhang Xiaohan , Kim Kyeong-Man
Published: January 2023

Background

Desensitization of G protein–coupled receptors (GPCRs) refers to a rapid attenuation of responsiveness that occurs with repeated or continuous exposure to agonists. GRK-mediated phosphorylation and subsequent binding with arrestins in the activated receptor cytoplasmic cavity in competition with G proteins has been suggested as the conventional mechanism of desensitization. Along with widely accepted conventional mechanism of desensitization, studies of various GPCRs including dopamine D2-like receptors (D2R, D3R, D4R) have suggested the existence of another desensitization mechanism. In this study, loss-of-function approaches and D2-like receptor mutants that display different desensitization properties were used to elucidate the molecular mechanisms responsible for desensitization.

Results

Desensitization development entailed the signaling cascade composed of Src, PDK1, and Akt, the latter of which in turn interacted with USP33, an arrestin deubiquitinase, to promote arrestin deubiquitination. The deubiquitinated arrestin subsequently formed a complex with Gβγ and translocated to the nucleus via an importin complex, wherein it sequestered Gβγ from the receptor and Gα, thereby attenuating receptor signaling. As in D2-like receptors, both USP33 and importin β1 were involved in the desensitization of the β2 adrenoceptor.

Conclusions

In addition to the conventional mechanism of desensitization, which occurs on the plasma membrane and in the cytosol, this study provides a new insight that another desensitization pathway in which nuclear trafficking plays a critical role is operating. It is plausible that multiple, complementary desensitization measures are in place to properly induce desensitization depending on receptor characteristics or the surrounding environment.
Role of Calcr expressing neurons in the medial amygdala in social contact among females
Authors: Fukumitsu Kansai , Huang Arthur J. , McHugh Thomas J. , Kuroda Kumi O.
Published: January 2023

Social animals become stressed upon social isolation, proactively engaging in affiliative contacts among conspecifics after resocialization. We have previously reported that calcitonin receptor (Calcr) expressing neurons in the central part of the medial preoptic area (cMPOA) mediate contact-seeking behaviors in female mice. Calcr neurons in the posterodorsal part of the medial amygdala (MeApd) are also activated by resocialization, however their role in social affiliation is still unclear. Here we first investigated the functional characteristics of MeApd Calcr + cells; these neurons are GABAergic and show female-biased Calcr expression. Next, using an adeno-associated virus vector expressing a short hairpin RNA targeting Calcr we aimed to identify its molecular role in the MeApd. Inhibiting Calcr expression in the MeApd increased social contacts during resocialization without affecting locomotor activity, suggesting that the endogenous Calcr signaling in the MeApd suppresses social contacts. These results demonstrate the distinct roles of Calcr in the cMPOA and MeApd for regulating social affiliation.
Large-scale genomic analysis of global Klebsiella pneumoniae plasmids reveals multiple simultaneous clusters of carbapenem-resistant hypervirulent strains
Authors: Spadar Anton , Perdigão João , Campino Susana , Clark Taane G.
Published: January 2023

Background

Klebsiella pneumoniae (Kp) Gram-negative bacteria cause nosocomial infections and rapidly acquire antimicrobial resistance (AMR), which makes it a global threat to human health. It also has a comparatively rare hypervirulent phenotype that can lead to severe disease in otherwise healthy individuals. Unlike classic Kp, canonical hypervirulent strains usually have limited AMR. However, after initial case reports in 2015, carbapenem-resistant hypervirulent Kp has increased in prevalence, including in China, but there is limited understanding of its burden  in other geographical regions.

Methods

Here, we examined the largest collection of publicly available sequenced Kp isolates (n=13,178), containing 1603 different sequence types (e.g. ST11 15.0%, ST258 9.5%), and 2174 (16.5%) hypervirulent strains. We analysed the plasmid replicons and carbapenemase and siderophore encoding genes to understand the movement of hypervirulence and AMR genes located on plasmids, and their convergence in carbapenem-resistant hypervirulent Kp.

Results

We identified and analysed 3034 unique plasmid replicons to inform the epidemiology and transmission dynamics of carbapenem-resistant hypervirulent Kp (n=1028, 7.8%). We found several outbreaks globally, including one involving ST11 strains in China and another of ST231 in Asia centred on India, Thailand, and Pakistan. There was evidence of global flow of Kp, including across multiple continents. In most cases, clusters of Kp isolates are the result of hypervirulence genes entering classic strains, instead of carbapenem resistance genes entering canonical hypervirulent ones.

Conclusions

Our analysis demonstrates the importance of plasmid analysis in the monitoring of carbapenem-resistant and hypervirulent strains of Kp. With the growing adoption of omics-based technologies for clinical and surveillance applications, including in geographical regions with gaps in data and knowledge (e.g. sub-Saharan Africa), the identification of the spread of AMR will inform infection control globally.
Does inflammation markers or treatment type moderate exercise intensity effects on changes in muscle strength in cancer survivors participating in a 6-month combined resistance- and endurance exercise program? Results from the Phys-Can trial
Authors: Henriksson Anna , Strandberg Emelie , Stenling Andreas , Mazzoni Anne-Sophie , Sjövall Katarina , Börjeson Sussanne , Raastad Truls , Demmelmaier Ingrid , Berntsen Sveinung , Nordin Karin
Published: January 2023

Background

Resistance exercise has a beneficial impact on physical function for patients receiving oncological treatment. However, there is an inter-individual variation in the response to exercise and the tolerability to high-intensity exercise. Identifying potential moderating factors, such as inflammation and treatment type, for changes in muscle strength is important to improve the effectiveness of exercise programs. Therefore, we aimed to investigate if inflammation and type of oncological treatment moderate the effects of exercise intensity (high vs. low-moderate) on muscular strength changes in patients with breast (BRCA) or prostate cancer (PRCA).

Methods

Participants with BRCA (n = 286) and PRCA (n = 65) from the Physical training and Cancer study (Phys-Can) were included in the present study. Participants performed a combined resistance- and endurance exercise program during six months, at either high or low-moderate intensity. Separate regression models were estimated for each cancer type, with and without interaction terms. Moderators included in the models were treatment type (i.e., neo/adjuvant chemotherapy—yes/no for BRCA, adjuvant androgen deprivation therapy (ADT)—yes/no for PRCA)), and inflammation (interleukin 6 (IL6) and tumor necrosis factor-alpha (TNFα)) at follow-up.

Results

For BRCA, neither IL6 (b = 2.469, 95% CI [− 7.614, 12.552]) nor TNFα (b = 0.036, 95% CI [− 6.345, 6.418]) levels moderated the effect of exercise intensity on muscle strength change. The same was observed for chemotherapy treatment (b = 4.893, 95% CI [− 2.938, 12.724]). Similarly, for PRCA, the effect of exercise intensity on muscle strength change was not moderated by IL6 (b = − 1.423, 95% CI [− 17.894, 15.048]) and TNFα (b = − 1.905, 95% CI [− 8.542, 4.732]) levels, nor by ADT (b = − 0.180, 95% CI [− 11.201, 10.841]).

Conclusions

The effect of exercise intensity on muscle strength is not moderated by TNFα, IL6, neo/adjuvant chemotherapy, or ADT, and therefore cannot explain any intra-variation of training response regarding exercise intensity (e.g., strength gain) for BRCA or PRCA in this setting.

Trial registration: ClinicalTrials.gov NCT02473003.
Acceptability and use of waist-worn physical activity monitors in Jamaican adolescents: lessons from the field
Authors: Smith Joanne A. , Christie Sara-Lou , Rockette-Wagner Bonny , Wilson Lorraine , Govia Ishtar O. , Facey Keri-Ann , Tulloch-Reid Marshall K.
Published: January 2023

Objective

We report our experience with a validated waist-worn activity monitor in Jamaican adolescents attending urban high schools. Seventy-nine adolescents from the Global Diet and Activity Research (GDAR) study, recruited from 5 urban Jamaican high schools (two coeducational (n = 37), two all-female schools (n = 32) and one all-boys school (n = 10)) were asked to wear Actigraph wGT3X-BT accelerometers for 7 days (24-h), removing the device only when bathing or swimming. They also logged wake up and bed times in an activity diary. Accelerometry was considered valid if at least 4 days with ≥ 10-h monitor wear were recorded. Validity was compared by adolescent demographic and school characteristics. We also reviewed the students’ written feedback on objective physical activity measurement.

Results

Participants, 80.5% female, had a mean age of 15.5 ± 0.8 years with 60% attending schools in low-income communities. Accelerometer return rates were > 98% with 84% providing valid data. Validity did not vary by age group, sex and school setting. While participants were excited about participating in the accelerometer sub-study, commonly reported challenges included monitor discomfort during sleep and maintaining the study diary. Objective measurement of physical activity using 24-h waist-worn accelerometers is feasible and acceptable in Jamaican adolescents.
Hypomethylation in MTNR1B: a novel epigenetic marker for atherosclerosis profiling using stenosis radiophenotype and blood inflammatory cells
Authors: Kim Jee Yeon , Jelinek Jaroslav , Lee Young Ho , Kim Dae Hyun , Kang Keunsoo , Ryu Su Hyun , Moon Hye Rin , Cho Kwangjo , Rha Seo Hee , Cha Jae Kwan , Issa Jean-Pierre J. , Kim Jei
Published: January 2023

Background

Changes in gene-specific promoter methylation may result from aging and environmental influences. Atherosclerosis is associated with aging and environmental effects. Thus, promoter methylation profiling may be used as an epigenetic tool to evaluate the impact of aging and the environment on atherosclerosis development. However, gene-specific methylation changes are currently inadequate epigenetic markers for predicting atherosclerosis and cardiovascular disease pathogenesis.

Results

We profiled and validated changes in gene-specific promoter methylation associated with atherosclerosis using stenosis radiophenotypes of cranial vessels and blood inflammatory cells rather than direct sampling of atherosclerotic plaques. First, we profiled gene-specific promoter methylation changes using digital restriction enzyme analysis of methylation (DREAM) sequencing in peripheral blood mononuclear cells from eight samples each of cranial vessels with and without severe-stenosis radiophenotypes. Using DREAM sequencing profiling, 11 tags were detected in the promoter regions of the ACVR1C, ADCK5, EFNA2, ENOSF1, GLS2, KNDC1, MTNR1B, PACSIN3, PAX8-AS1, TLDC1, and ZNF7 genes. Using methylation evaluation, we found that EFNA2, ENOSF1, GLS2, KNDC1, MTNR1B, PAX8-AS1, and TLDC1 showed > 5% promoter methylation in non-plaque intima, atherosclerotic vascular tissues, and buffy coats. Using logistic regression analysis, we identified hypomethylation of MTNR1B as an independent variable for the stenosis radiophenotype prediction model by combining it with traditional atherosclerosis risk factors including age, hypertension history, and increases in creatinine, lipoprotein (a), and homocysteine. We performed fivefold cross-validation of the prediction model using 384 patients with ischemic stroke (50 [13%] no-stenosis and 334 [87%] > 1 stenosis radiophenotype). For the cross-validation, the training dataset included 70% of the dataset. The prediction model showed an accuracy of 0.887, specificity to predict stenosis radiophenotype of 0.940, sensitivity to predict no-stenosis radiophenotype of 0.533, and area under receiver operating characteristic curve of 0.877 to predict stenosis radiophenotype from the test dataset including 30% of the dataset.

Conclusions

We identified and validated MTNR1B hypomethylation as an epigenetic marker to predict cranial vessel atherosclerosis using stenosis radiophenotypes and blood inflammatory cells rather than direct atherosclerotic plaque sampling.