bluuebunny/crossref_metadata_2025 huggingface dataset:
A vault-prediction formula for implantable collamer lens based on preoperative parameters: a retrospective clinical study
Authors: Yang Jing , Li Hui , Wu Minhui , He Runzhang , Nong Yating , Zou Zongyin , Zhang Chun , Zhou Sheng
Published: August 2023

Objectives

The aim of the present study was to predict the vault of implantable collamer lens (ICL) using a formula established based on the preoperative parameters.

Methods

This retrospective study included data on 226 eyes from 114 patients(the median age and range was 27.5 ± 5.7; 18–46 years) who underwent EVO-ICL surgery between May 2021 and April 2022. Preoperative parameters, such as anterior chamber depth (ACD) horizontal angle-to-angle diameter (ATA), Crystalline lens rise (CLR), and vault (1 week after surgery) were measured by anterior segment optical coherence tomography. The axial length of eyes (AL) and white-to-white (WTW) values were measured using an IOLmaster and calipers under a slit lamp separately.

Result

The mean WTW, ACD, horizontal ATA diameter, CLR, AL, and vault 1 week after surgery were 11.42 ± 0.37 mm, 3.25 ± 0.25 mm, 11.72 ± 0.44 mm, 45.78 ± 175.42 μm, 27.61 ± 1.93 mm, and 586.51 ± 254.54 μm respectively. Multivariate regression analysis showed that the ICL-width, ACD (β = 0.293), ATA (β =-0.657), CLR (β =-0.157), and the anterior chamber angle in temporal side (T:ACA) (β=-0.277) were predictors of the vault size (adjusted-R2 = 0.39, P < 0.001).

Conclusion

The formula built based on these preoperative parameters could be used to predict the vault before surgery. The predictors indicated that the pre-operative parameters of eye such as ACD, ATA, CLR and T:ACA play an important role in choosing optimal ICL size.
Leucine-rich glioma-inactivated protein 1 antibody-associated encephalitis in a 22-month-old girl: a case report
Authors: Zhao JiaChang , Yu XiaoMing , Qu GuangLi , Wang ShuQi , Wang YanJun
Published: August 2023

Background

LGI-1 antibody-associated encephalitis is a type of autoimmune encephalitis with a lower prevalence than NMDAR antibody-associated encephalitis. LGI-1 antibody-associated encephalitis is the second most prevalent of all autoimmune encephalitides. LGI-1 antibodies interfere with the interactions of inter-synaptic proteins to produce clinical manifestations (N Engl J Med 378:840–851, 2018).

Case presentation

Leucine-rich glioma-inactivated protein 1 (LGI-1) antibody-associated encephalitis is a subtype of autoimmune encephalitis with a low incidence. We report a case of a girl aged 22 months with convulsive seizures, psycho-behavioral abnormalities, sleep disorders, and limb tremors. This patient was diagnosed with LGI-1 antibody-associated encephalitis based on electroencephalography (EEG) examinations and autoimmune encephalitis antibody analyses. A combined therapy of anti-epileptic and immunosuppressant drugs was effective in controlling the patient’s neurological symptoms.

Conclusions

The incidence of LGI-1 antibody-associated encephalitis is low and it occurs mostly in middle-aged and elderly patients, although it occasionally occurs in pediatric patients. To the best of our knowledge, this report describes the youngest patient with LGI-1 antibody-associated encephalitis. Following timely diagnosis, administration of anti-epileptic and immunosuppressant therapy was remarkably effective.
Prevalence and factors associated with suicidal ideation, cannabis, and alcohol use during the COVID-19 pandemic in Saskatchewan: findings from a joint-effect modeling
Authors: Adeyinka Daniel A. , Novik Nuelle , Novotna Gabriela , Bartram Mary , Gabrys Robert , Muhajarine Nazeem
Published: August 2023

Background

Generally, pandemics such as COVID-19 take an enormous toll on people’s lives. As the pandemic now turns to an endemic state, growing attention has been paid to the multiple adverse mental health and behavioral issues, such as suicidal ideation and substance use. However, the interplay of suicidality and substance misuse during the pandemic has been limited. We aimed to investigate the prevalence of co-occurrence of suicide ideation, alcohol and cannabis misuse, and the factors that are associated with these co-occurrences in the province of Saskatchewan during the COVID-19 pandemic.

Methods

We performed a multivariable trivariate probit regression on a sample of 666 Saskatchewan adolescents and adults (16 years or older), drawn from the cycle 10 data collection (March 2022) of the Mental Health Commission of Canada, and Canadian Centre on Substance Use and Addiction (MHCC-CCSA) dataset.

Results

The prevalence of suicidal ideation was higher among respondents who reported both problematic cannabis and alcohol use (25.8%) than single users of alcohol (23.2%) and cannabis (18.7%). Younger respondents (16–34 years) and those who reported recent changes in other substance use were independent factors that were associated with the common experience of suicide ideation, problematic cannabis, and alcohol use. Having a diagnosis of mental health disorders either before or during the pandemic, and the perceived inability to bounce back after the pandemic (low resilience) are strong correlates of suicidal ideation. Those who lived alone, between 35 and 55 years of age were more likely to report problematic alcohol use. Those who reported changes in alternative activities, who reported pandemic stress, and declared a LGBTQIA2S + identity had higher probability of problematic cannabis use.

Conclusions

As the pandemic persists, improving access to suicide and substance use interventions for the vulnerable groups identified in this study may be impactful.
Drug-induced interstitial lung disease caused by olaparib: three case reports and review of the Japanese Adverse Drug Event Report database and literature
Authors: Ishimoto Hiroshi , Sakamoto Noriho , Kido Takashi , Ozasa Mutsumi , Tsutsui Shin , Mori Mayako , Setoguchi Daichi , Takemoto Shinnosuke , Obase Yasushi , Ishimatsu Yuji , Tomonaga Chiharu , Matsumoto Kanako , Morisaki Sachiko , Miura Kiyonori , Mukae Hiroshi
Published: August 2023

Background

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has demonstrated effectiveness in treating ovarian, breast, and other cancers, particularly those with specific molecular subtypes including, but not limited to, BRCA1/2 mutations. Consequently, its utilization is expected to increase in the future. For this reason, it is important to acknowledge the potential for adverse events associated with olaparib, including the relatively rare but significant risk of drug-induced interstitial lung disease (DIILD). Since DIILD can lead to fatal outcomes, its early detection is crucial. The dissemination of knowledge regarding DIILD can be facilitated through case reports; however, specific reports of DIILD caused by olaparib have only been published in Japanese. To the best of our knowledge, this is the first report in English of our experience with three cases of DIILD caused by olaparib.

Case presentation

Cases 1, 2, and 3 involved Japanese women with ovarian cancer who had been receiving olaparib at a dose of 600 mg/day. Case 1, a 72-year-old woman who had been on olaparib for 4 months, and case 2, a 51-year-old woman who had been on olaparib for 8 months, reported fever and general malaise. Chest computed tomography (CT) revealed pale ground glass opacity (GGO) similar to hypersensitivity pneumonitis. The severity grade was 2 in both cases. Case 3, a 78-year-old woman who had been on olaparib for 3 weeks, presented with cough and reported dyspnea on exertion. Chest CT revealed non-specific interstitial pneumonia and organizing pneumonia-like shadows. The severity grade was 4. Olaparib was discontinued in all cases. Case 1 received 0.6 mg/kg of prednisolone due to mild hypoxia, while prednisolone was not administered in case 2 due to the absence of hypoxia. Case 3 received steroid pulse therapy due to severe hypoxia. Olaparib administration was not resumed in any patient.

Conclusion

DIILD caused by olaparib in Japan, including the present three cases, commonly presents with GGO, similar to hypersensitivity pneumonitis on chest CT. The prognosis for the majority of patients is favorable; however, there have been instances of severe cases. Early recognition of drug-induced lung injury and further accumulation of cases is important.
3D simulation of percutaneous sustentaculum tali screw insertion in calcaneal fractures
Authors: Li Xian. , Wang Xiao-ke. , Yu Lian-kui. , Zhang Chao. , Zhao Ming-ming. , Yan Jun. , Han Li-ren.
Published: August 2023

Background

In calcaneal fractures, the percutaneous screw fixation (PSF) is currently considered to be the better choice, but it is difficult to accurately place the screw into the sustentaculum tali (ST) during the operation. In this study, the ideal entry point, angle, diameter and length of the screw were calculated by simulating the operation process.

Methods

We retrospectively collected the calcaneus computed tomography (CT) scans of 180 adults, DICOM-formatted CT-scan images of each patient were imported into Mimics software to establish calcaneus model. Virtual screws were placed on the lateral of the posterior talar articular surface (PTAS), the lateral edge of the anterior process of calcaneus (APC), and the calcaneal tuberosity, respectively, the trajectory and size of the screws were calculated.

Results

The mean maximum diameter of the PTAS screw was 42.20 ± 3.71 mm. The vertical distance between the midpoint of the APC optimal screw trajectory and the lowest point of the tarsal sinus was 10.67 ± 1.84 mm, and the distance between the midpoint of the APC optimal screw trajectory and the calcaneocuboid joint was 5 mm ~ 19.81 ± 2.08 mm. The mean maximum lengths of APC screws was 44.69 ± 4.81 mm, and the Angle between the screw and the coronal plane of the calcaneus from proximal to distal was 4.72°±2.15° to 20.52°±3.77°. The optimal point of the maximum diameter of the calcaneal tuberosity screw was located at the lateral border of the achilles tendon endpoint. The mean maximum diameters of calcaneal tuberosity screws was 4.46 ± 0.85 mm, the mean maximum lengths of screws was 65.31 ± 4.76 mm. We found gender-dependent differences for the mean maximum diameter and the maximum length of the three screws.

Conclusions

The study provides effective positioning for percutaneous screw fixation of calcaneal fractures. For safer and more efficient screw placement, we suggest individualised preoperative 3D reconstruction simulations. Further biomechanical studies are needed to verify the function of the screw.
Lentinula Edodes Mycelia extract regulates the function of antigen-presenting cells to activate immune cells and prevent tumor-induced deterioration of immune function
Authors: Kajiyama Shota , Nagatake Takahiro , Ishikawa Satoru , Hosomi Koji , Shimada Yuki , Matsui Yasunori , Kunisawa Jun
Published: August 2023

Immune cell activation is essential for cancer rejection; however, the tumor microenvironment leads to deterioration of immune function, which enables cancer cells to survive and proliferate. We previously reported that oral ingestion of Lentinula Edodes Mycelia (L.E.M.) extract enhances the tumor antigen-specific T-cell response and exerts an antitumor effect in a tumor-bearing mouse model. In this study, we focused on antigen-presenting cells (APCs) located upstream of the immune system, induced a T-cell response, then examined the impact of L.E.M. extract on the APCs. L.E.M. extract enhanced the expression of MHC-I, MHC-II, CD86, CD80, and CD40 in bone marrow-derived dendritic cells (DCs) and strongly induced the production of IL-12. L.E.M.-stimulated DCs enhanced IFN-γ production from CD8+ T cells and induced their differentiation into effector cells. Furthermore, L.E.M. extract promoted IL-12 production and suppressed the production of IL-10 and TGF-β by transforming bone marrow-derived macrophages into M1-like macrophages. Furthermore, in a B16F10 melanoma inoculation model, DCs in the spleen were decreased and their activation was suppressed by the presence of cancer; however, ingestion of L.E.M. extract prevented this functional deterioration of DCs. In the spleen of cancer-bearing mice, the number of CD11b− F4/80+ macrophages in a hypoactivated state was also increased, whereas L.E.M. extract suppressed the increase of such macrophages. These findings suggest that L.E.M. extract may exhibit an antitumor immune response by regulating the function of APCs to induce cytotoxic T lymphocytes, as well as by suppressing the decline in antigen-presenting cell activity caused by the presence of cancer.
Major influencing factors on routine implementation of shared decision-making in cancer care: qualitative process evaluation of a stepped-wedge cluster randomized trial
Authors: Hahlweg Pola , Lindig Anja , Frerichs Wiebke , Zill Jördis , Hanken Henning , Müller Volkmar , Peters Mia-Carlotta , Scholl Isabelle
Published: August 2023

Background

Shared decision-making (SDM) is highly relevant in oncology but rarely implemented in routine care. In a stepped-wedge cluster randomized implementation trial, the outcome evaluation of a theoretically and empirically based multi-component SDM implementation program did not show a statistically significant effect on patient-reported SDM uptake. Within this SDM implementation trial, a thorough a priori planned process evaluation was conducted. Thus, the aim of this study was to investigate factors influencing SDM implementation in the context of a multi-component SDM implementation program.

Methods

We conducted qualitative process evaluation of a stepped-wedge SDM implementation trial. Qualitative data included interviews with nurses and physicians of participating departments, field notes by the study team, and meeting minutes. Data were analyzed via deductive and inductive qualitative content analysis on basis of the Consolidated Framework for Implementation Research (CFIR).

Results

Transcripts of 107 interviews with 126 nurses and physicians, 304 pages of field note documentation, and 125 pages of meeting minutes were analyzed. Major factors influencing SDM implementation were found for all domains of the CFIR: a) four regarding characteristics of the individuals involved (e.g., perceived personal relevance, individual motivation to change), b) eleven regarding the inner setting (e.g., leadership engagement, networks and communication, available resources, compatibility with clinical practice), c) two regarding the outer setting (e.g., culture of health care delivery), d) eight regarding characteristics of the intervention (e.g., relative advantage, adaptability), and e) three regarding the implementation process (e.g., integration into existing structures). Furthermore, we found strong interrelations between several of the influencing factors within and between domains.

Conclusions

This comprehensive process evaluation complements the outcome evaluation of the SDM implementation trial and adds to its interpretation. The identified influencing factors can be used for planning, conducting, and evaluating SDM implementation in the future.

Trial registration

clinicaltrials.gov, NCT03393351, registered 8 January 2018, https://clinicaltrials.gov/ct2/show/NCT03393351
Short- and long-term direct and indirect costs of illness after ostomy creation – a Swedish nationwide registry study
Authors: Carlsson Eva , Forsmark Annabelle , Sternhufvud Catarina , Scheffel Gina , Andersen Frederikke B. , Persson Eva I
Published: August 2023

Background

Despite advance in care of people with an ostomy, related complications remain prevalent. The objective of this study was to examine short- and long-term healthcare resource utilization and associated costs after ostomy creation.

Methods

This observational study was based on retrospectively collected data from national and regional Swedish registries. The population consisted of people living in Sweden, who had an ostomy created. The earliest index date was 1 January 2006, and people were followed for ten years, until death, reversal of temporary ostomy, termination of purchases of ostomy products, or end of study, which was 31 December 2019. Each person with an ostomy was matched with two controls from the general population based on age, gender, and region.

Results

In total, 40,988 persons were included: 19,645 with colostomy, 16,408 with ileostomy, and 4,935 with urostomy. The underlying diseases for colostomy and ileostomy creations were primarily bowel cancer, 50.0% and 55.8% respectively, and additionally inflammatory bowel disease for 20.6% of ileostomies. The underlying cause for urostomy creation was mainly bladder cancer (85.0%). In the first year after ostomy creation (excl. index admission), the total mean healthcare cost was 329,200 SEK per person with colostomy, 330,800 SEK for ileostomy, and 254,100 SEK for urostomy (100 SEK was equivalent to 9.58 EUR). Although the annual mean healthcare cost decreased over time, it remained significantly elevated compared to controls, even after 10 years, with hospitalization being the main cost driver. The artificial opening was responsible for 19.3–22.8% of 30-day readmissions after ostomy creation and for 19.7–21.4% of hospitalizations during the entire study period. For the ileostomy group, dehydration was responsible for 13.0% of 30-day readmissions and 4.5% of hospitalization during the study period.

Conclusions

This study reported a high disease burden for persons with an ostomy. This had a substantial impact on the healthcare cost for at least ten years after ostomy creation. Working ability seemed to be negatively impacted, indicated by increased cost of sickness absence and early retirement. This calls for improved management and support of ostomy care for the benefit of the affected persons and for the cost of society.
Regulatory changes associated with the head to trunk developmental transition
Authors: Duarte Patrícia , Brattig Correia Rion , Nóvoa Ana , Mallo Moisés
Published: August 2023

Background

Development of vertebrate embryos is characterized by early formation of the anterior tissues followed by the sequential extension of the axis at their posterior end to build the trunk and tail structures, first by the activity of the primitive streak and then of the tail bud. Embryological, molecular and genetic data indicate that head and trunk development are significantly different, suggesting that the transition into the trunk formation stage involves major changes in regulatory gene networks.

Results

We explored those regulatory changes by generating differential interaction networks and chromatin accessibility profiles from the posterior epiblast region of mouse embryos at embryonic day (E)7.5 and E8.5. We observed changes in various cell processes, including several signaling pathways, ubiquitination machinery, ion dynamics and metabolic processes involving lipids that could contribute to the functional switch in the progenitor region of the embryo. We further explored the functional impact of changes observed in Wnt signaling associated processes, revealing a switch in the functional relevance of Wnt molecule palmitoleoylation, essential during gastrulation but becoming differentially required for the control of axial extension and progenitor differentiation processes during trunk formation. We also found substantial changes in chromatin accessibility at the two developmental stages, mostly mapping to intergenic regions and presenting differential footprinting profiles to several key transcription factors, indicating a significant switch in the regulatory elements controlling head or trunk development. Those chromatin changes are largely independent of retinoic acid, despite the key role of this factor in the transition to trunk development. We also tested the functional relevance of potential enhancers identified in the accessibility assays that reproduced the expression profiles of genes involved in the transition. Deletion of these regions by genome editing had limited effect on the expression of those genes, suggesting the existence of redundant enhancers that guarantee robust expression patterns.

Conclusions

This work provides a global view of the regulatory changes controlling the switch into the axial extension phase of vertebrate embryonic development. It also revealed mechanisms by which the cellular context influences the activity of regulatory factors, channeling them to implement one of several possible biological outputs.
Appraising the causal relationship between plasma caffeine levels and neuropsychiatric disorders through Mendelian randomization
Authors: Woolf Benjamin , Cronjé Héléne T. , Zagkos Loukas , Burgess Stephen , Gill Dipender , Larsson Susanna C.
Published: August 2023

Background

Caffeine exposure modifies the turnover of monoamine neurotransmitters, which play a role in several neuropsychiatric disorders. We conducted a Mendelian randomization study to investigate whether higher plasma caffeine levels are causally associated with the risk of anorexia nervosa, bipolar disorder, major depressive disorder (MDD), and schizophrenia.

Methods

Summary-level data on the neuropsychiatric disorders were obtained from large-scale genome-wide association studies (GWASs) of European ancestry participants (n = 72,517 to 807,553) and meta-analyzed with the corresponding data from the FinnGen study (n = 356,077). Summary-level data on plasma caffeine were extracted from a GWAS meta-analysis of 9876 European ancestry individuals. The Mendelian randomization analyses estimated the Wald ratio for each genetic variant and meta-analyzed the variant-specific estimates using multiplicative random effects meta-analysis.

Results

After correcting for multiple testing, genetically predicted higher plasma caffeine levels were associated with higher odds of anorexia nervosa (odds ratio [OR] = 1.124; 95% confidence interval [CI] = 1.024–1.238, pFDR = 0.039) and a lower odds of bipolar disorder (OR = 0.905, 95% CI = 0.827–0.929, pFDR = 0.041) and MDD (OR = 0.965, 95% CI = 0.937–0.995, pFDR = 0.039). Instrumented plasma caffeine levels were not associated with schizophrenia (OR = 0.986, 95% CI = 0.929–1.047, pFDR = 0.646).

Conclusions

These Mendelian randomization findings indicate that long-term higher plasma caffeine levels may lower the risk of bipolar disorder and MDD but increase the risk of anorexia nervosa. These results warrant further research to explore whether caffeine consumption, supplementation, or abstinence could render clinically relevant therapeutic or preventative psychiatric effects.
Effect of home-based online training and activity feedback on oxygen uptake in patients after surgical cancer therapy: a randomized controlled trial
Authors: Falz Roberto , Bischoff Christian , Thieme René , Tegtbur Uwe , Hillemanns Peter , Stolzenburg Jens-Uwe , Aktas Bahriye , Bork Ulrich , Weitz Jürgen , Lässing Johannes , Leps Christian , Voß Johannes , Lordick Florian , Schulze Antina , Gockel Ines , Busse Martin
Published: August 2023

Background

Exercise training is beneficial in enhancing physical function and quality of life in cancer patients. Its comprehensive implementation remains challenging, and underlying cardiopulmonary adaptations are poorly investigated. This randomized controlled trial examines the implementation and effects of home-based online training on cardiopulmonary variables and physical activity.

Methods

Of screened post-surgical patients with breast, prostate, or colorectal cancer, 148 were randomly assigned (1:1) to an intervention (2 × 30 min/week of strength-endurance training using video presentations) and a control group. All patients received activity feedback during the 6-month intervention period. Primary endpoint was change in oxygen uptake after 6 months. Secondary endpoints included changes in cardiac output, rate pressure product, quality of life (EORTC QoL-C30), C-reactive protein, and activity behavior.

Results

One hundred twenty-two patients (62 intervention and 60 control group) completed the study period. Change in oxygen uptake between intervention and control patients was 1.8 vs. 0.66 ml/kg/min (estimated difference after 6 months: 1.24; 95% CI 0.23 to 2.55; p = 0.017). Rate pressure product was reduced in IG (estimated difference after 6 months: − 1079; 95% CI − 2157 to − 1; p = 0.05). Physical activity per week was not different in IG and CG. There were no significant interaction effects in body composition, cardiac output, C-reactive protein, or quality of life.

Conclusions

Home-based online training among post-surgery cancer patients revealed an increase of oxygen uptake and a decrease of myocardial workload during exercise. The implementation of area-wide home-based training and activity feedback as an integral component in cancer care and studies investigating long-term effects are needed.

Trial registration

DRKS-ID: DRKS00020499; Registered 17 March 2020.
The pathways from disadvantaged socioeconomic status in childhood to edentulism in mid-to-late adulthood over the life-course
Authors: Zhang Xiaoning , Dai Shuping , Jiang Xue , Huang Wenhao , Zhou Qiong , Wang Sheng
Published: August 2023

Background

This study aimed to examine the direct and indirect pathways from childhood socioeconomic status (SES) to the prevalence of edentulism in mid-to-late age Chinese individuals using structural equation modeling (SEM).

Methods

This study analyzed data from 17,032 mid- to-late age Chinese individuals in the 2014 and 2015 China Health and Retirement Longitudinal Study (CHARLS). Childhood SES was determined based on the parents’ education and occupation, financial situation of the family, primary residence, food availability, and medical convenience. Adulthood SES was established according to educational achievements of the individuals. Edentulism is defined as the loss of all natural teeth. SEM was used to examine the statistical significance of the association between childhood SES and edentulism, mediated by childhood health, adulthood SES, and adult health.

Results

Childhood SES had significant indirect (β = -0.026, p < 0.01), and total (β = -0.040, p < 0.01) effects on edentulism. It was determined that 65% of the total effect of childhood SES on edentulism was indirect, and mainly mediated by adult SES. Also, the goodness-of-fit indices of the best-fitting model were acceptable.

Conclusion

This study revealed that childhood health, adult health and adult SES are mediators that explain the relationship between childhood SES and edentulism. The global attention to alleviate the inequality in edentulism should focus on exploring recommendations and intervention strategies from childhood to adulthood, by considering adult SES, childhood and adult health.
Unpacking racism during COVID-19: narratives from racialized Canadian gay, bisexual, and queer men
Authors: Grey Cornel , Tian Ian Liujia , Skakoon-Sparling Shayna , Daroya Emerich , Klassen Ben , Lessard David , Gaspar Mark , Sinno Jad , Sang Jordan M. , Perez-Brumer Amaya , Lachowsky Nathan J. , Moore David M. , Jollimore Jody , Hart Trevor A. , Cox Joseph , Grace Daniel
Published: August 2023

Objective

Epidemics impact individuals unevenly across race, gender, and sexuality. In addition to being more vulnerable to COVID-19 infection, evidence suggests racialized gender and sexual minorities experienced disproportionate levels of discrimination and stigma during the COVID-19 epidemic. Drawing on Critical Race Theory (CRT), we examined the experiences of gay, bisexual, queer, and other men who have sex with men (GBQM) of colour facing discrimination during COVID-19.

Design

Engage-COVID-19 is a mixed methods study examining the impact of COVID-19 on GBQM living in Vancouver, Toronto, and Montréal, Canada. We conducted two rounds of qualitative interviews (November 2020 to February 2021, and June to October 2021) with 93 GBQM to explore the evolving impact of COVID-19 on their lives. Transcripts were coded using inductive thematic analysis. Data analysis was conducted using Nvivo software.

Results

Fifty-nine participants identified as Black, Indigenous, and/or a Person of Colour (BIPOC). These GBQM of colour described multiple experiences of discrimination during COVID-19. Although participants did not report experiences of discrimination based on their sexual identity during COVID-19, we found that experiences of racism affected how they were treated within their sexual networks. Experiences of racism were most often reported by East Asian and Black GBQM. These participants faced racism in public and online spaces, primarily in the form of verbal harassment. Several participants were also harassed because they wore face masks. Verbal abuse against GBQM of colour was largely prompted by racist discourses related to COVID-19.

Conclusion

Racism remains a pernicious threat to the well-being of GBQM of colour. CRT highlights the importance of assessing how sexualized and gendered discourses about race shape the experiences of GBQM of colour navigating multiple epidemics like COVID-19 and HIV. These pervasive discourses unevenly affect racial and sexual minorities across multiple epidemics, and negatively impact health outcomes for these populations.
Exosome-sheathed ROS-responsive nanogel to improve targeted therapy in perimenopausal depression
Authors: Hu Yue , Zhao Min , Wang Hui , Guo Yang , Cheng Xiaolan , Zhao Tong , Wang Hanqing , Zhang Yafeng , Ma Yong , Tao Weiwei
Published: August 2023

The development of natural membranes as coatings for nanoparticles to traverse the blood-brain barrier (BBB) presents an effective approach for treating central nervous system (CNS) disorders. In this study, we have designed a nanogel loaded with PACAP and estrogen (E2), sheathed with exosomes and responsive to reactive oxygen species (ROS), denoted as HA NGs@exosomes. The objective of this novel design is to serve as a potent drug carrier for the targeted treatment of perimenopausal depression. The efficient cellular uptake and BBB penetration of HA NGs@exosomes has been demonstrated in vitro and in vivo. Following intranasal intervention with HA NGs@exosomes, ovariectomized mice under chronic unpredictable mild stress (CUMS) have shown improved behavioral performance, indicating that HA NGs@exosomes produced a rapid-onset antidepressant effect. Moreover, HA NGs@exosomes exhibit notable antioxidant and anti-inflammatory properties and may regulate the expression of pivotal proteins in the PACAP/PAC1 pathway to promote synaptic plasticity. Our results serve as a proof-of-concept for the utility of exosome-sheathed ROS-responsive nanogel as a promising drug carrier for the treatment of perimenopausal depression.

Graphical Abstract
Conversion of senescent cartilage into a pro-chondrogenic microenvironment with antibody-functionalized copper sulfate nanoparticles for efficient osteoarthritis therapy
Authors: Wang Xianming , Cai Yu , Wu Cuixi , Liang Jiamin , Tang Kangning , Lin Zefeng , Chen Lingling , Lu Yao , Wang Qing
Published: August 2023

The development of osteoarthritis (OA) correlates with the expansion of senescent cells in cartilage, which contributes to an inflammatory microenvironment that accelerates matrix degradation and hampers cartilage generation. To address OA, we synthesized small copper sulfide nanoparticles functionalized with anti-beta-2-microglobulin antibodies (B2M-CuS NPs) that catalyze the formation of toxic •OH from H2O2 via peroxidase-like activity. These B2M-CuS NPs are specifically targeted to induce apoptosis in senescent chondrocytes while showing no toxicity toward normal chondrocytes. Furthermore, B2M-CuS NPs enhance the chondrogenesis of normal chondrocytes. Thus, B2M-CuS NPs can effectively treat OA by clearing senescent chondrocytes and promoting cartilage regeneration after intra-articular injection into the knee joints of surgery-induced OA mice. This study uses smart nanomaterials to treat OA with a synergistic strategy that both remodels senescent cartilage and creates a pro-chondrogenic microenvironment.
Clinical outcomes of parenchymal-sparing versus anatomic resection for colorectal liver metastases: a systematic review and meta-analysis
Authors: Wang Kun , Liu Yin , Hao Mengdi , Li Huimin , Liang Xiaoqing , Yuan Dajin , Ding Lei
Published: August 2023

Background

The advantages of parenchymal-sparing resection (PSR) over anatomic resection (AR) of colorectal liver metastases (CRLM) remain controversial. Here, we aim to evaluate their safety and efficacy.

Methods

A systematic review and meta-analysis of short-term perioperative outcomes and long-term oncological outcomes for PSR and AR were performed by searching Pubmed, Embase, the Cochrane Library and Web of Science databases.

Results

Twenty-two studies were considered eligible (totally 7228 patients: AR, n = 3154 (43.6%) vs. PSR, n = 4074 (56.4%)). Overall survival (OS, HR = 1.08, 95% CI: 0.95-1.22, P = 0.245) and disease-free survival (DFS, HR = 1.09, 95% CI: 0.94-1.28, P = 0.259) were comparable between the two groups. There were no significant differences in 3-year OS, 5-year OS, 3-year DFS, 5-year DFS, 3-year liver recurrence-free survival (liver-RFS) and 5-year liver-RFS. In terms of perioperative outcome, patients undergoing AR surgery were associated with prolonged operation time (WMD = 51.48 min, 95% CI: 29.03-73.93, P < 0.001), higher amount of blood loss (WMD = 189.92 ml, 95% CI: 21.39-358.45, P = 0.027), increased intraoperative blood transfusion rate (RR = 2.24, 95% CI: 1.54-3.26, P < 0.001), prolonged hospital stay (WMD = 1.00 day, 95% CI: 0.34-1.67, P = 0.003), postoperative complications (RR = 2.28, 95% CI: 1.88-2.77, P < 0.001), and 90-day mortality (RR = 3.08, 95% CI: 1.88-5.03, P < 0.001). While PSR surgery was associated with positive resection margins (RR = 0.77, 95% CI: 0.61-0.97, P = 0.024), intrahepatic recurrence (RR = 0.90, 95% CI: 0.82-0.98, P = 0.021) and repeat hepatectomy (RR = 0.64, 95% CI: 0.55-0.76, P < 0.001).

Conclusion

Considering relatively acceptable heterogeneity, PSR had better perioperative outcomes without compromising oncological long-term outcomes. However, these findings must be carefully interpreted, requiring more supporting evidence.

Trial registration

PROSPERO registration number: CRD42023445332.
A novel radiographic analysis system for subaxial cervical spine pedicle screw placement
Authors: Ding Baozhi , Zhou Tangjun , Ma Hui , Zhao Jie
Published: August 2023

Background

Precise pedicle screw placement of the subaxial cervical spine is difficult. Not every hospital is equipped with a guidance system that can provide effective help. Computed tomography (CT) scanning is almost a routine preoperative examination for cervical spine surgery in all hospitals. Appropriate measurement and analysis of the CT images could assist optimal cervical pedicle screw placement. The purpose of this study is to propose a new and universal method using computed tomography (CT) morphological parameters analysis to assist optimal cervical pedicle screw placement from C3 to C7.

Methods

A localization system with six parameters was designed based on preoperative CT reconstruction to guide subaxial cervical spine pedicle screw placement. The six parameters were distance from the starting point to the midline [D1], distance from the starting point to the lower edge of the inferior articular process [D2], transverse section angle [TSA], sagittal section angle [SSA], pedicle width [PW], and pedicle height [PH]. The six parameters were analyzed in 53 participants.

Results

Combining D1 and D2 could localize the entrance of the pedicle screw, and we concluded that D1 and TSA and D2 and SSA could be a new standard for determination of the transverse and sagittal orientation of the pedicle screw. The six parameters were closely related to the patient’s gender, height, and weight. PH and PW were linearly correlated and could guide selection of the appropriate pedicle screw. SSA was an independent parameter of the relevant vertebral body, and changes in SSA had nothing to do with the curvature or posture of the cervical spine.

Conclusions

Understanding and applying the six-parameter localization system are essential for achieving accurate and optimal pedicle screw placement in subaxial cervical spine, regardless of cervical sagittal alignment.
Specific detection of tau seeding activity in Alzheimer’s disease using rationally designed biosensor cells
Authors: Lathuiliere Aurelien , Jo Youhwa , Perbet Romain , Donahue Cameron , Commins Caitlin , Quittot Noé , Fan Zhanyun , Bennett Rachel E. , Hyman Bradley T.
Published: August 2023

Background

The prion-like propagation of tau in neurodegenerative disorders implies that misfolded pathological tau can recruit the normal protein and template its aggregation. Here, we report the methods for the development of sensitive biosensor cell lines for the detection of tau seeding activity.

Results

We performed the rational design of novel tau probes based on the current structural knowledge of pathological tau aggregates in Alzheimer’s disease. We generated Förster resonance energy transfer (FRET)-based biosensor stable cell lines and characterized their sensitivity, specificity, and overall ability to detect bioactive tau in human samples. As compared to the reference biosensor line, the optimized probe design resulted in an increased efficiency in the detection of tau seeding. The increased sensitivity allowed for the detection of lower amount of tau seeding competency in human brain samples, while preserving specificity for tau seeds found in Alzheimer’s disease.

Conclusions

This next generation of FRET-based biosensor cells is a novel tool to study tau seeding activity in Alzheimer’s disease human samples, especially in samples with low levels of seeding activity, which may help studying early tau-related pathological events.
Reconstruction of the last bacterial common ancestor from 183 pangenomes reveals a versatile ancient core genome
Authors: Hyun Jason C. , Palsson Bernhard O.
Published: August 2023

Background

Cumulative sequencing efforts have yielded enough genomes to construct pangenomes for dozens of bacterial species and elucidate intraspecies gene conservation. Given the diversity of organisms for which this is achievable, similar analyses for ancestral species are feasible through the integration of pangenomics and phylogenetics, promising deeper insights into the nature of ancient life.

Results

We construct pangenomes for 183 bacterial species from 54,085 genomes and identify their core genomes using a novel statistical model to estimate genome-specific error rates and underlying gene frequencies. The core genomes are then integrated into a phylogenetic tree to reconstruct the core genome of the last bacterial common ancestor (LBCA), yielding three main results: First, the gene content of modern and ancestral core genomes are diverse at the level of individual genes but are similarly distributed by functional category and share several poorly characterized genes. Second, the LBCA core genome is distinct from any individual modern core genome but has many fundamental biological systems intact, especially those involving translation machinery and biosynthetic pathways to all major nucleotides and amino acids. Third, despite this metabolic versatility, the LBCA core genome likely requires additional non-core genes for viability, based on comparisons with the minimal organism, JCVI-Syn3A.

Conclusions

These results suggest that many cellular systems commonly conserved in modern bacteria were not just present in ancient bacteria but were nearly immutable with respect to short-term intraspecies variation. Extending this analysis to other domains of life will likely provide similar insights into more distant ancestral species.
Elicitation of T-cell-derived IFN-γ-dependent immunity by highly conserved Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII)
Authors: Ren Zhenyu , Shi Qiyang , Xu Simin , Xu Jiahui , Yin Yi , Lin Zhijie , Xu Sui , Ma Xiaoqin , Liu Yaobao , Zhu Guoding , He Xinlong , Lu Jingyuan , Li Yinyue , Zhang Wenwen , Liu Jiali , Yang Yun , Han Eun-Taek , Cao Jun , Lu Feng
Published: August 2023

Background

Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII) is an essential ligand for reticulocyte recognition and host cell invasion by P. ovale curtisi. However, the genomic variation, antigenicity and immunogenicity of PocDBP-RII remain major knowledge gaps.

Methods

A total of 93 P. ovale curtisi samples were collected from migrant workers who returned to China from 17 countries in Africa between 2012 and 2016. The genetic polymorphism, natural selection and copy number variation (CNV) were investigated by sequencing and real-time PCR. The antigenicity and immunogenicity of the recombinant PocDBP-RII (rPocDBP-RII) protein were further examined, and the humoral and cellular responses of immunized mice were assessed using protein microarrays and flow cytometry.

Results

Efficiently expressed and purified rPocDBP-RII (39 kDa) was successfully used as an antigen for immunization in mice. The haplotype diversity (Hd) of PocDBP-RII gene was 0.105, and the nucleotide diversity index (π) was 0.00011. No increased copy number was found among the collected isolates of P. ovale curtisi. Furthermore, rPocDBP-RII induced persistent antigen-specific antibody production with a serum IgG antibody titer of 1: 16,000. IFN-γ-producing T cells, rather than IL-10-producing cells, were activated in response to the stimulation of rPocDBP-RII. Compared to PBS-immunized mice (negative control), there was a higher percentage of CD4+CD44highCD62L− T cells (effector memory T cells) and CD8+CD44highCD62L+ T cells (central memory T cells) in rPocDBP-RII‑immunized mice.

Conclusions

PocDBP-RII sequences were highly conserved in clinical isolates of P. ovale curtisi. rPocDBP-RII protein could mediate protective blood-stage immunity through IFN-γ-producing CD4+ and CD8+ T cells and memory T cells, in addition to inducing specific antibodies. Our results suggested that rPocDBP-RII protein has potential as a vaccine candidate to provide assessment and guidance for malaria control and elimination activities.

Graphical Abstract
Bacterial ventriculoperitoneal shunt infections: changing trends in antimicrobial susceptibility, a 7-year retrospective study from Pakistan
Authors: Akram Asif Amina , Mahmood Khalid , Riaz Saba , McHugh Timothy , Sultan Sikander
Published: August 2023

Background

Ventriculoperitoneal (VP) shunt infections in adults represent a severe complication and make treatment more challenging. Therefore, drug susceptibility patterns are crucial for therapeutic decisions and infection control in neurosurgical centers. This 7-year retrospective study aimed to identify the bacteria responsible for adult VP shunt infections and determine their drug susceptibility patterns.

Methods

This single-center study was performed from 2015 to 2021 in Lahore, Pakistan, and included CSF cultures from VP shunt infections. Demographic data, causative organisms, and antimicrobial susceptibility testing results were collected. Multivariate analysis of variance (MANOVA) and two-sample t-tests were used to analyze and compare the antibiotic sensitivity trends over the study period.

Results

14,473 isolates recovered from 13,937 CSF samples of VP shunt infections were identified and analyzed for their susceptibility patterns to antimicrobials. The proportion of Gram-negative and Gram-positive bacteria were 11,030 (76%) and 3443 (24)%, respectively. The predominant bacteria were Acinetobacter species (n = 5898, 41%), followed by Pseudomonas species (n = 2368, 16%) and coagulase-negative Staphylococcus (CoNS) (n = 1880, 13%). 100% of Staphylococcus aureus (S.aureus) and CoNS were sensitive to vancomycin and linezolid (n = 2580). However, 52% of S. aureus (719/1,343) were methicillin-resistant Staphylococcus aureus (MRSA). Acinetobacter showed maximum sensitivity to meropenem at 69% (2759/4768). Pseudomonas was 80% (1385/1863 sensitive to piperacillin-tazobactam, Escherichia coli (E. coli) showed 72% to amikacin (748/1055), while Klebsiella spp. was 57% (574/1170) sensitive to piperacillin-tazobactam. The sensitivity of piperacillin-tazobactam and meropenem for Gram-negative bacteria decreased significantly (p < 0.05) over 7 years, with 92.2% and 88.91% sensitive in 2015 and 66.7% and 62.8% sensitive in 2021, respectively.

Conclusion

The significant decrease in the effectiveness of carbapenem and beta-lactam/beta-lactamase inhibitor combination drugs for the common Gram-negative causative agents of VP shunt infections suggests that alternative antibiotics such as colistin, fosfomycin, ceftazidime/avibactam, ceftolozane/tazobactam, and tigecycline should be considered and in consequence included in testing panels. Additionally, it is recommended to adopt care bundles for the prevention of VP shunt infection.
Identification of GRIN2D as a novel therapeutic target in pancreatic ductal adenocarcinoma
Authors: Wang Jiatong , Wong Chi Hin , Zhu Yinxin , Yao Xiaoqiang , Ng Kelvin K C , Zhou Chengzhi , To Ka Fai , Chen Yangchao
Published: August 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a dismal prognosis, and despite significant advances in our understanding of its genetic drivers, like KRAS, TP53, CDKN2A, and SMAD4, effective therapies remain limited. Here, we identified a new therapeutic target GRIN2D and then explored its functions and mechanisms in PDAC progression.

Methods

We performed a genome-wide RNAi screen in a PDAC xenograft model and identified GRIN2D, which encodes the GluN2D subunit of N-methyl-D-aspartate receptors (NMDARs), as a potential oncogene. Western blot, immunohistochemistry, and analysis on Gene Expression Omnibus were used for detecting the expression of GRIN2D in PDAC. Cellular experiments were conducted for exploring the functions of GRIN2D in vitro while subcutaneous and orthotopic injections were used in in vivo study. To clarify the mechanism, we used RNA sequencing and cellular experiments to identify the related signaling pathway. Cellular assays, RT-qPCR, and western blot helped identify the impacts of the NMDAR antagonist memantine.

Results

We demonstrated that GRIN2D was highly expressed in PDAC cells, and further promoted oncogenic functions. Mechanistically, transcriptome profiling identified GRIN2D-regulated genes in PDAC cells. We found that GRIN2D promoted PDAC progression by activating the p38 MAPK signaling pathway and transcription factor CREB, which in turn promoted the expression of HMGA2 and IL20RB. The upregulated GRIN2D could effectively promote tumor growth and liver metastasis in PDAC. We also investigated the therapeutic potential of NMDAR antagonism in PDAC and found that memantine reduced the expression of GRIN2D and inhibited PDAC progression.

Conclusion

Our results suggested that NMDA receptor GRIN2D plays important oncogenic roles in PDAC and represents a novel therapeutic target.