bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer testis antigen burden (CTAB): a novel biomarker of tumor-associated antigens in lung cancer
Authors: Seager R. J. , Senosain Maria-Fernanda , Van Roey Erik , Gao Shuang , DePietro Paul , Nesline Mary K. , Dash Durga Prasad , Zhang Shengle , Ko Heidi , Hastings Stephanie B. , Strickland Kyle C. , Previs Rebecca A. , Jensen Taylor J. , Eisenberg Marcia , Caveney Brian J. , Severson Eric A. , Ramkissoon Shakti , Conroy Jeffrey M. , Pabla Sarabjot
Published: February 2024

Background

Cancer-testis antigens (CTAs) are tumor antigens that are normally expressed in the testes but are aberrantly expressed in several cancers. CTA overexpression drives the metastasis and progression of lung cancer, and is associated with poor prognosis. To improve lung cancer diagnosis, prognostic prediction, and drug discovery, robust CTA identification and quantitation is needed. In this study, we examined and quantified the co-expression of CTAs in lung cancer to derive cancer testis antigen burden (CTAB), a novel biomarker of immunotherapy response.

Methods

Formalin fixed paraffin embedded (FFPE) tumor samples in discovery cohort (n = 5250) and immunotherapy and combination therapy treated non-small cell lung cancer (NSCLC) retrospective (n = 250) cohorts were tested by comprehensive genomic and immune profiling (CGIP), including tumor mutational burden (TMB) and the mRNA expression of 17 CTAs. PD-L1 expression was evaluated by IHC. CTA expression was summed to derive the CTAB score. The median CTAB score for the discovery cohort of 170 was applied to the retrospective cohort as cutoff for CTAB “high” and “low”. Biomarker and gene expression correlation was measured by Spearman correlation. Kaplan–Meier survival analyses were used to detect overall survival (OS) differences, and objective response rate (ORR) based on RECIST criteria was compared using Fisher’s exact test.

Results

The CTAs were highly co-expressed (p < 0.05) in the discovery cohort. There was no correlation between CTAB and PD-L1 expression (R = 0.011, p = 0.45) but some correlation with TMB (R = 0.11, p = 9.2 × 10–14). Kaplan–Meier survival analysis of the immunotherapy-treated NSCLC cohort revealed better OS for the pembrolizumab monotherapy treated patients with high CTAB (p = 0.027). The combination group demonstrated improved OS compared to pembrolizumab monotherapy group (p = 0.04). The pembrolizumab monotherapy patients with high CTAB had a greater ORR than the combination therapy group (p = 0.02).

Conclusions

CTA co-expression can be reliably measured using CGIP in solid tumors. As a biomarker, CTAB appears to be independent from PD-L1 expression, suggesting that CTAB represents aspects of tumor immunogenicity not measured by current standard of care testing. Improved OS and ORR for high CTAB NSCLC patients treated with pembrolizumab monotherapy suggests a unique underlying aspect of immune response to these tumor antigens that needs further investigation.
“They call me the ‘Great Queen’”: implementing the Malkia Klabu program to improve access to HIV self-testing and contraception for adolescent girls and young women in Tanzania
Authors: Willard-Grace Rachel , Abigail Cabrera F. , Bykhovsky Camilla , Douglas Kayla , Hunter Lauren A. , Mnyippembe Agatha , Mgunya Kassim Hassan , McCoy Sandra I. , Liu Jenny X.
Published: February 2024

Background

Adolescent girls and young woman (AGYW) comprise a significant proportion of new HIV infections and unintended pregnancies in sub-Saharan Africa yet face many barriers to accessing family planning and reproductive health (FPRH) information and services. Developed via human-centered design, the Malkia Klabu (“Queen Club”) program aimed to facilitate access to HIV self-testing (HIVST) and FPRH information and products at privately-owned drug shops. We sought to understand barriers and facilitators to program implementation in a 4-month pilot in Tanzania.

Methods

Forty semi-structured interviews were conducted with participants in a cluster randomized trial of the Malkia Klabu program from November 2019 through March 2020, including 11 with AGYW, 26 with drug shopkeepers, and three with counselors at health facilities to whom AGYW were referred. Interviews were audio-recorded, transcribed, coded, and analyzed to identify key themes. The Consolidated Framework for Implementation Research (CFIR) was used to assess barriers and facilitators to program implementation at multiple levels. CFIR considers the outer setting (e.g., culture and systemic conditions), the inner setting where the intervention is implemented (e.g., incentives, relationships, and available resources), the individuals involved, the innovation as it relates to stakeholder needs, and the implementation process.

Results

The Malkia Klabu program reshaped and directed the role of drug shopkeepers as providers of information and resources rather than FPRH gatekeepers. Key implementation facilitators included the program’s adaptability to a wide range of needs and stages of readiness among AGYW, ability to capitalize on AGYW social networks for driving membership, responsiveness to AGYW’s need for privacy, and positive contributions to the income and community standing of drug shopkeepers. Components such as HIVST were highly acceptable to both AGYW and shopkeepers, and the introduction of the loyalty program and HIVST kits in shops opened doors to the provision of FPRH products and information, which was further facilitated by program tools such as videos, product displays, and symbol cards. Although some shopkeepers maintained beliefs that certain contraceptive methods were inappropriate for AGYW, most appeared to provide the products as part of the program.

Conclusions

The Malkia Klabu intervention's success was due in part to its ability to address key motivations of both AGYW and drug shopkeepers, such as maintaining privacy and increasing access to FPRH products for AGYW and increasing business for shops. Better understanding these implementation barriers and facilitators can inform the program’s future adaptation and scale-up.

Trial registration: clinicaltrials.gov #NCT04045912.
Validation of a modified version of the gross motor function measure in PPPR5D related neurodevelopmental disorder
Authors: Kanner Cara H. , Uher David , Zreibe Kyle , Beard Gabriella , Patterson Madison , Harris Matthew , Doerger Jerome , Calamia Sean , Chung Wendy K. , Montes Jacqueline
Published: February 2024

Background

Protein phosphatase 2 regulatory subunit B’ Delta (PPP2R5D)-related neurodevelopmental disorder is a rare genetic condition caused by pathogenic variants in the PPP2R5D gene. Clinical signs include hypotonia, gross motor delay, intellectual disability (ID), epilepsy, speech delays, and abnormal gait among other impairments. As this disorder was recognized within the last decade, there are only 103 people published diagnoses to date. A thorough understanding of the motor manifestations of this disorder has not yet been established. Knowledge of the natural history of PPP2R5D related neurodevelopmental disorder will lead to improved standard of care treatments as well as serve as a baseline foundation for future clinical trials. Appropriate outcome measures are necessary for use in clinical trials to uniformly measure function and monitor potential for change. The aim of this study was to validate the gross motor function measure (GMFM) in children and adults with PPP2R5D-related neurodevelopmental disorder in order to better characterize the disorder.

Results

Thirty-eight individuals with PPP2R5D pathogenic variants, median age 8.0 years (range 1–27) were evaluated. Gross motor, upper limb and ambulatory function were assessed using the GMFM-66, six-minute walk test (6MWT), 10-meter walk run (10MWR), timed up and go (TUG), and revised upper limb module (RULM). The pediatric disability inventory computer adapted test (PEDI-CAT) captured caregiver reported assessment. Median GMFM-66 score was 60.6 (SD = 17.3, range 21.1–96.0). There were strong associations between the GMFM-66 and related mobility measures, 10MWR (rs = −0.733; p < 0.001), TUG (rs= −0.747; p = 0.003), 6MWT (r = 0.633; p = 0.006), RULM (r = 0.763; p < 0.001), PEDICAT-mobility (r = 0.855; p < 0.001), and daily activities (r = 0.822; p < 0.001) domains.

Conclusions

The GMFM is a valid measure for characterizing motor function in individuals with PPP2R5D related neurodevelopmental disorder. The GMFM-66 had strong associations with the RULM and timed function tests which characterized gross motor, upper limb and ambulatory function demonstrating concurrent validity. The GMFM-66 was also able to differentiate between functional levels in PPP2R5D related neurodevelopmental disorder demonstrating discriminant validity. Future studies should examine its sensitivity to change over time, ability to identify sub-phenotypes, and suitability as an outcome measure in future clinical trials in individuals with PPP2R5D variants.
Are better AI algorithms for breast cancer detection also better at predicting risk? A paired case–control study
Authors: Santeramo Ruggiero , Damiani Celeste , Wei Jiefei , Montana Giovanni , Brentnall Adam R.
Published: February 2024

Background

There is increasing evidence that artificial intelligence (AI) breast cancer risk evaluation tools using digital mammograms are highly informative for 1–6 years following a negative screening examination. We hypothesized that algorithms that have previously been shown to work well for cancer detection will also work well for risk assessment and that performance of algorithms for detection and risk assessment is correlated.

Methods

To evaluate our hypothesis, we designed a case-control study using paired mammograms at diagnosis and at the previous screening visit. The study included n = 3386 women from the OPTIMAM registry, that includes mammograms from women diagnosed with breast cancer in the English breast screening program 2010–2019. Cases were diagnosed with invasive breast cancer or ductal carcinoma in situ at screening and were selected if they had a mammogram available at the screening examination that led to detection, and a paired mammogram at their previous screening visit 3y prior to detection when no cancer was detected. Controls without cancer were matched 1:1 to cases based on age (year), screening site, and mammography machine type. Risk assessment was conducted using a deep-learning model designed for breast cancer risk assessment (Mirai), and three open-source deep-learning algorithms designed for breast cancer detection. Discrimination was assessed using a matched area under the curve (AUC) statistic.

Results

Overall performance using the paired mammograms followed the same order by algorithm for risk assessment (AUC range 0.59–0.67) and detection (AUC 0.81–0.89), with Mirai performing best for both. There was also a correlation in performance for risk and detection within algorithms by cancer size, with much greater accuracy for large cancers (30 mm+, detection AUC: 0.88–0.92; risk AUC: 0.64–0.74) than smaller cancers (0 to < 10 mm, detection AUC: 0.73–0.86, risk AUC: 0.54–0.64). Mirai was relatively strong for risk assessment of smaller cancers (0 to < 10 mm, risk, Mirai AUC: 0.64 (95% CI 0.57 to 0.70); other algorithms AUC 0.54–0.56).

Conclusions

Improvements in risk assessment could stem from enhancing cancer detection capabilities of smaller cancers. Other state-of-the-art AI detection algorithms with high performance for smaller cancers might achieve relatively high performance for risk assessment.
Patients with obesity have more inflamed joints and higher CRP levels during the disease course in ACPA-positive RA but not in ACPA-negative RA
Authors: Hollander N. K. den , Boeren A. M. P , van der Helm-van Mil A. H. M. , van Steenbergen H. W.
Published: February 2024

Background

Obese RA patients have higher disease activity scores (DAS). Previous research showed that obese RA patients have higher tender joint count (TJC) and VAS general health. However, it remains unclear whether DAS components measuring local and systemic inflammation (swollen joint count (SJC), CRP) are increased and if this is present in the total RA population or confined to an ACPA subgroup. As ACPA is suggested to enhance inflammatory responses, we hypothesized that the association of obesity with SJC and CRP is present especially in ACPA-positive RA. We therefore studied associations of obesity with courses of DAS components in ACPA subgroups.

Methods

We studied 649 RA patients (291 ACPA-positive), included in the Leiden Early Arthritis Clinic. Five-year courses of DAS44 and DAS44 components (SJC—44, TJC—53, CRP, VAS (0–100)) were compared between RA patients with normal weight (BMI 18.5–24.9), overweight (25.0–29.9), and obesity (≥ 30.0), stratified for ACPA. Linear/Poisson mixed models with a knot at 4 months were used.

Results

Obese RA patients had + 0.32 higher DAS compared to normal weight during the 5-year follow-up. In ACPA-positive RA, obese patients had + 0.43 (95% CI: 0.22, 0.64) higher DAS, whereas in ACPA-negative RA, this difference was smaller and not statistically significant: + 0.19 (95% CI: − 0.01, 0.38). In ACPA-positive RA, all DAS components were significantly higher in obese patients compared to normal weight: SJC + 60% (IRR1.60; 95% CI: 1.18, 2.16), CRP + 3.7 mg/L (95% CI:0.95, 6.53), TJC + 55% (IRR1.55; 95% CI:1.15, 2.10), and VAS + 9 (95% CI: 4.0, 14.2). ACPA-negative obese RA patients tended to have higher TJC (IRR1.22; 95% CI: 0.96, 1.55) and VAS (β4.3; 95% CI: − 0.4, 9.0), while SJC (IRR1.07; 95% CI:0.85, 1.33) and CRP (β0.24; 95% CI: − 1.29, 3.32) were unaffected.

Conclusion

The association of obesity with a worse DAS course is mainly present in ACPA-positive RA; especially SJC and CRP levels remain higher in ACPA-positive RA patients with obesity but not ACPA-negative RA patients. This is the first demonstration that obesity influences the disease course of ACPA-positive and ACPA-negative RA differently.
Radiological complete response with regorafenib for multiple lung metastases of ascending colon cancer: a case report
Authors: Kikuchi Koji , Ogawa Masaaki , Sasaki Akira
Published: February 2024

Background

Regorafenib is an oral diphenylurea multikinase inhibitor and currently approved for use following third-line therapy for metastatic colorectal cancer (CRC) patients. Only one case has previously been reported of metastatic CRC showing a complete response (CR) to regorafenib.

Case presentation

A 68-year-old Japanese man underwent laparoscopy-assisted ileocecal resection and D3 lymphadenectomy due to his ascending colon cancer. Eighteen months after surgery, a laparoscopic hepatic left lateral segmentectomy was performed due to a liver tumor, and a pathological diagnosis of colorectal liver metastasis was made. Three months after the second surgery, contrast-enhanced computed tomography (CT) revealed multiple lung metastases. The patient had undergone 18 courses of the FOLFOX + bevacizumab chemotherapy regimen as their first-line therapy and 11 courses of the FOLFIRI + ramucirumab chemotherapy regimen as their second-line therapy. As their third-line therapy, the patient was administered the regorafenib chemotherapy regimen. We evaluated the chemotherapy treatment’s effect on the lung tumors by CT after 3, 7, 11, and 17 courses of the regorafenib chemotherapy regimen, finding that the lung tumors had shrunk with time; thus, each tumor was considered a partial response (PR) based on the RECIST guidelines. After 21 courses of the regorafenib chemotherapy regimen, the chemotherapy was discontinued in response to the patient’s wishes. Even at 1 and 3 months after the discontinuation of the chemotherapy, CT revealed that the lung tumors had shrunk, with each considered a PR. Furthermore, 9 months after the discontinuation of the chemotherapy, CT revealed scarring of the lung tumors. This was considered a CR, rather than a PR. The patient remains disease-free 18 months after the discontinuation of chemotherapy.

Conclusions

In this paper, we present the second case of radiological CR with regorafenib for multiple lung metastases of ascending colon cancer. Currently, there is no consensus on a treatment strategy for patients with radiological CR.
Natural compounds and mesenchymal stem cells: implications for inflammatory-impaired tissue regeneration
Authors: Li Wen , Xiang Zichao , Yu Wenjing , Huang Xiaobin , Jiang Qian , Abumansour Arwa , Yang Ying , Chen Chider
Published: February 2024

Inflammation is a common and important pathological process occurring in any part of the body and relating to a variety of diseases. Effective tissue repair is critical for the survival of impaired organisms. Considering the side effects of the currently used anti-inflammatory medications, new therapeutic agents are urgently needed for the improvement of regenerative capacities of inflammatory-impaired tissues. Mesenchymal stromal stem/progenitor cells (MSCs) are characterized by the capabilities of self-renewal and multipotent differentiation and exhibit immunomodulatory capacity. Due to the ability to modulate inflammatory phenotypes and immune responses, MSCs have been considered as a potential alternative therapy for autoimmune and inflammatory diseases. Natural compounds (NCs) are complex small multiple-target molecules mostly derived from plants and microorganisms, exhibiting therapeutic effects in many disorders, such as osteoporosis, diabetes, cancer, and inflammatory/autoimmune diseases. Recently, increasing studies focused on the prominent effects of NCs on MSCs, including the regulation of cell survival and inflammatory response, as well as osteogenic/adipogenic differentiation capacities, which indicate the roles of NCs on MSC-based cytotherapy in several inflammatory diseases. Their therapeutic effects and fewer side effects in numerous physiological processes, compared to chemosynthetic drugs, made them to be a new therapeutic avenue combined with MSCs for impaired tissue regeneration. Here we summarize the current understanding of the influence of NCs on MSCs and related downstream signaling pathways, specifically in pathological inflammatory conditions. In addition, the emerging concepts through the combination of NCs and MSCs to expand the therapeutic perspectives are highlighted. A promising MSC source from oral/dental tissues is also discussed, with a remarkable potential for MSC-based therapy in future clinical applications.
Grafted human-induced pluripotent stem cells-derived oligodendrocyte progenitor cells combined with human umbilical vein endothelial cells contribute to functional recovery following spinal cord injury
Authors: Li Qian , Liu Sumei , Zheng Tianqi , Li Mo , Qi Boling , Zhou Liping , Liu Bochao , Ma Dan , Zhao Chao , Chen Zhiguo
Published: February 2024

Background

Spinal cord injury (SCI) is a devastating disease that causes extensive damage to oligodendrocytes and neurons leading to demyelination and axonal degeneration. In this study, we co-transplanted cell grafts containing oligodendrocyte progenitor cells (OPCs) derived from human-induced pluripotent stem cells (iPSCs) combined with human umbilical vein endothelial cells (HUVECs), which were reported to promote OPCs survival and migration, into rat contusion models to promote functional recovery after SCI.

Methods

OPCs were derived from iPSCs and identified by immunofluorescence at different time points. Functional assays in vitro were performed to evaluate the effect of HUVECs on the proliferation, migration, and survival of OPCs by co-culture and migration assay, as well as on the neuronal axonal growth. A combination of OPCs and HUVECs was transplanted into the rat contusive model. Upon 8 weeks, immunofluorescence staining was performed to test the safety of transplanted cells and to observe the neuronal repairment, myelination, and neural circuit reconstruction at the injured area; also, the functional recovery was assessed by Basso, Beattie, and Bresnahan open-field scale, Ladder climb, SEP, and MEP. Furthermore, the effect of HUVECs on grafts was also determined in vivo.

Results

Data showed that HUVECs promote the proliferation, migration, and survival of OPCs both in vitro and in vivo. Furthermore, 8 weeks upon engraftment, the rats with OPCs and HUVECs co-transplantation noticeably facilitated remyelination, enhanced functional connection between the grafts and the host and promoted functional recovery. In addition, compared with the OPCs-alone transplantation, the co-transplantation generated more sensory neurons at the lesion border and significantly improved the sensory functional recovery.

Conclusions

Our study demonstrates that transplantation of OPCs combined with HUVECs significantly enhances both motor and sensory functional recovery after SCI. No significance was observed between OPCs combined with HUVECs group and OPCs-alone group in motor function recovery, while the sensory function recovery was significantly promoted in OPCs combined with HUVECs groups compared with the other two groups. These findings provide novel insights into the field of SCI research.
Lp quasi-norm minimization: algorithm and applications
Authors: Sleem Omar M. , Ashour M. E. , Aybat N. S. , Lagoa Constantino M.
Published: February 2024

Sparsity finds applications in diverse areas such as statistics, machine learning, and signal processing. Computations over sparse structures are less complex compared to their dense counterparts and need less storage. This paper proposes a heuristic method for retrieving sparse approximate solutions of optimization problems via minimizing the $$\ell _{p}$$

ℓ
p

quasi-norm, where $$0<p<1$$

0
<
p
<
1

. An iterative two-block algorithm for minimizing the $$\ell _{p}$$

ℓ
p

quasi-norm subject to convex constraints is proposed. The proposed algorithm requires solving for the roots of a scalar degree polynomial as opposed to applying a soft thresholding operator in the case of $$\ell _{1}$$

ℓ
1

norm minimization. The algorithm’s merit relies on its ability to solve the $$\ell _{p}$$

ℓ
p

quasi-norm minimization subject to any convex constraints set. For the specific case of constraints defined by differentiable functions with Lipschitz continuous gradient, a second, faster algorithm is proposed. Using a proximal gradient step, we mitigate the convex projection step and hence enhance the algorithm’s speed while proving its convergence. We present various applications where the proposed algorithm excels, namely, sparse signal reconstruction, system identification, and matrix completion. The results demonstrate the significant gains obtained by the proposed algorithm compared to other $$\ell _{p}$$

ℓ
p

quasi-norm based methods presented in previous literature.
DNA damage response alterations in clear cell renal cell carcinoma: clinical, molecular, and prognostic implications
Authors: Jing Xiao , Qin Xiangcheng , Liu Hao , Liu Huanhuan , Wang Huina , Qin Jiayue , Zhang Yanui , Cao Shanbo , Fan Xiaodong
Published: February 2024

Background

DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic responses. Nonetheless, the characteristics and significance of DDR alterations in clear cell renal cell carcinoma (ccRCC) remain undefined. This study aimed to explore the predictive role, molecular mechanism, and tumor immune profile of DDR genes in ccRCC.

Methods

We prospectively sequenced 757 tumors and matched blood DNA samples from Chinese patients with ccRCC using next-generation sequencing (NGS) and analyzed data from 537 patients from The Cancer Genome Atlas (TCGA). A comprehensive analysis was performed.

Results

Fifty-two percent of Chinese patients with ccRCC harbored DDR gene mutations and 57% of TCGA patients. The immunotherapy treatment prognosis of patients with DDR gene mutations was superior to that of patients without DDR gene mutations (p = 0.047). DDR gene mutations were associated with more gene mutations and a higher tumor mutation load (TMB, p < 0.001). Moreover, patients with DDR gene mutations have a distinct mutational signature compared with those with wild-type DDR. Furthermore, the DDR-mut group had elevated neoantigen load (including single-nucleotide variants (SNV) and indel neoantigen load, p = 0.037 and p = 0.002, respectively), TCR Shannon (p = 0.025), and neutrophils (p = 0.010). DDR gene mutations exhibited a distinct immune profile with significantly higher expression levels of TNFSF9, CD70, ICAM1, and indoleamine-2,3-dioxygenase (IDO) and lower expression levels of VTCN1 and IL12A.

Conclusions

Our data suggest that the detection of somatic mutations in DDR genes can predict the efficacy of immunotherapy in patients with ccRCC. Furthermore, we revealed the unique molecular and immune mechanisms underlying ccRCC with DDR gene mutations.
Study protocol for a randomized controlled trial testing the efficacy of Emotion Detectives In-Out: a blended version of the unified protocol for transdiagnostic treatment of emotional disorders in Portuguese children
Authors: Moreira Helena , Skvarc Dave , Gomes-Pereira Bárbara , Albuquerque Alzira , Góis Ana Carolina , Fonseca Ana , Pereira Ana Maria , Caiado Brígida , Paulino Bruna , Santos Catarina , Ehrenreich-May Jill , Canavarro Maria Cristina , Saraiva Mariana , Vicente Vitória Nunes , Pereira Ana Isabel
Published: February 2024

Background

Childhood emotional disorders (EDs; i.e., anxiety and depressive disorders) are currently a public health concern. Their high prevalence, long-term effects, and profound influence on the lives of children and families highlight the need to identify and treat these disorders as early and effectively as possible. This clinical trial will examine the efficacy of a blended version (i.e., combining face-to-face and online sessions into one treatment protocol) of the Unified Protocol for Children (the “Emotion Detectives In–Out” program). This program is a manualized cognitive-behavioral therapy for the transdiagnostic treatment of EDs in children aged 7 to 12 years that aims to reduce the intensity and frequency of strong and aversive emotional experiences by helping children learn how to confront those emotions and respond to them in more adaptive ways.

Methods

This study is designed as a multicenter equivalence randomized controlled parallel-group two-arm trial comparing the Emotion Detectives In–Out program with an evidenced-based group intervention for children with anxiety disorders (the Coping Cat program). Participants will be children aged between 7 and 12 years with an anxiety disorder or with clinically significant anxiety symptoms as well as one of their parents or a legal representative. A minimum sample size of 138 children (69 per group) is needed to test whether the efficacy of the proposed intervention is equivalent to that of the well-established Coping Cat intervention.

Discussion

We expect Emotion Detectives In–Out to be a feasible and efficacious alternative intervention for treating children's EDs by allowing for a greater increase in children's access to care. A blended format is expected to overcome common barriers to treatment (e.g., parents´ lack of time to attend regular sessions) and make the intervention more accessible to families.

Trial registration

The clinical trial is registered at ClinicalTrials.gov (Identifier: NCT05747131, date assigned February 28, 2023).
Transcription factor BACH1 in cancer: roles, mechanisms, and prospects for targeted therapy
Authors: Hu Dian , Zhang Zerui , Luo Xiangyuan , Li Siwen , Jiang Junqing , Zhang Jiaqian , Wu Zhangfan , Wang Yijun , Sun Mengyu , Chen Xiaoping , Zhang Bixiang , Xu Xiao , Wang Shuai , Xu Shengjun , Wang Yufei , Huang Wenjie , Xia Limin
Published: February 2024

Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap ‘n’ Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status of BACH1 in malignant tumor behaviors, and summarize its role in immune regulation in cancer. Moreover, this review focuses on the potential of BACH1 as a novel therapeutic target and prognostic biomarker. Notably, the mechanisms underlying the roles of BACH1 in ferroptosis, oxidative stress and tumor microenvironment remain to be explored. BACH1 has a dual impact on cancer, which affects the accuracy and efficiency of targeted drug delivery. Finally, the promising directions of future BACH1 research are prospected. A systematical and clear understanding of BACH1 would undoubtedly take us one step closer to facilitating its translation from basic research into the clinic.
Navigating the digital world: development of an evidence-based digital literacy program and assessment tool for youth
Authors: Buchan M. Claire , Bhawra Jasmin , Katapally Tarun Reddy
Published: February 2024

The rapid expansion of digital connectivity has provided youth with wide-ranging access to digital platforms for communication, entertainment, and education. In light of this profound shift, there have been growing concerns about online safety, data privacy, and cybersecurity. A critical factor influencing the ability of youth to responsibly navigate digital platforms is digital literacy. While digital literacy programs have been implemented in various regions worldwide, significant disparities remain not only in overall digital literacy levels, but also the assessment of digital literacy initiatives. To address these challenges, an environmental scan and literature review were conducted to identify existing digital literacy programs in Canada developed specifically for youth, as well as digital literacy assessment tools, respectively. The search encompassed peer-reviewed articles, organizational curricula, and assessment measures indexed in various databases and organization websites. The environmental scan identified 15 programs targeting key components of digital literacy such as data safety, cyberbullying, and digital media. The literature review identified 12 digital literacy assessment tools. Based on the findings, data were synthesized from shortlisted programs and assessment tools to inform the development of both a new digital literacy program and assessment tool to complement the youth-focused program. The new program focuses on four key components: (1) digital fluency, (2) digital privacy and safety, (3) ethics and empathy, and (4) consumer awareness. A 15-item assessment tool was also developed consisting of 4–5 questions specific to each program component. Given the growing importance of digital competencies, a youth-focused program and assessment tool are crucial for understanding and addressing digital literacy among this vulnerable cohort. This program's adaptability allows for customization across sociodemographic target groups, including culturally diverse and geographically remote communities—an aspect that has the potential to enhance digital literacy across settings. Implementing digital literacy programs can better prepare youth for an increasingly digital world, while minimizing potential risks associated with technology use.
Ambient noise multimode surface wave tomography
Authors: Nishida Kiwamu , Takagi Ryota , Takeo Akiko
Published: February 2024

Seismic techniques using earthquakes are powerful tools for exploring the Earth’s internal structure. However, the earthquake distribution limits the spatial resolution. In recent years, ambient noise surface wave tomography using ambient seismic wave field has resolved these limitations. A typical ambient seismic wave field is microseisms excited by ocean swell activities. Ambient noise surface wave tomography is a technique in seismic interferometry that extracts seismic wave propagation between pairs of stations by cross-correlating the seismic records. The cross-correlation function can be interpreted as an impulsive response at a station with a virtual source at the other station. This technique became standard with the development of modern dense seismic networks. This paper reviews a theory of seismic interferometry for ambient noise surface wave tomography and procedures for practical data processing to calculate cross-correlation functions. The tomographic method typically consists of four steps: (1) the construction of reference 1-D models, (2) phase velocity measurements for each path, (3) 2-D phase velocity inversions, and (4) the construction of a 3-D S-wave tomographic model obtained from series of local 1-D inversions at all the grids. This paper presents the feasibility of multimode surface wave dispersion measurements for improving depth resolution.
Co-expression analysis of transcriptomic data from cancer and healthy specimens reveals rewiring of proteasome genes and an interaction with the XPO1 gene across several tumour types
Authors: Spataro Vito , Buetti-Dinh Antoine
Published: February 2024

Background

The 26S proteasome is a large intracellular multiprotein complex, that plays a homeostatic role by degrading proteins that have been tagged by ubiquitin. It is composed of 64 subunits assembled according to a well-defined structure and stoichiometry. Several proteasome subunits have been found to be overexpressed in tumours. However, comprehensive data are lacking on the relative abundance of each subunit and the impact on proteasome composition or stoichiometry. In cancer treatment, proteasome inhibitors and inhibitors of XPO1 (Exportin-1) have unexpectedly a similar range of activity, but the interaction between the two pathways has not been studied.

Methods

We performed gene co-expression analysis of 38 genes encoding proteasome subunits and 38 genes encoding proteins involved in nucleocytoplasmic transport in specimens from the Cancer Genome Atlas (33 tumour types) and from the Gene Tissue Expression database (32 healthy tissue types). We obtained 65 matrices, each containing Pearson correlation factors for 2964 gene pairs. We applied cluster analysis to the correlation matrices and compared the distribution of Pearson correlation coefficients of thirteen tumour types with their healthy tissue counterpart.

Results

Strong positive correlation (R Pearson correlation > 0.8) was observed for pairs of proteasome genes in the majority of healthy tissues, whereas the correlation for co-expression was significantly lower (R ≤ 0.50) for most gene pairs in the majority of cancer types. Cluster analysis based on gene co-expression allowed to distinguish cancers from healthy tissues in a clear-cut manner, and to identify the genes that contributed most to the separation. The crossed analysis between proteasome and nucleocytoplasmic transport genes showed that the expression of XPO1 and a subset of proteasome genes, including in particular PSMD14, is correlated in several cancer types and not in their healthy counterpart.

Conclusions

This analysis reveals that in cancer the co-expression of proteasome genes is significantly altered, highlighting the genes that are more often deregulated. In addition, it finds that XPO1 expression is often correlated with the expression of proteasome genes. From a therapeutic perspective, these findings support the investigation of novel targets within the proteasome and strategies of co-targeting of the proteasome and nucleocytoplasmic transport.
Sustainable biocontrol of purple blotch disease in Allium cepa L. by biocontrol yeasts, Pichia kluyveri and Filobasidium wieringae
Authors: Abo-Elyousr Kamal A. M. , Imran Muhammad , Sallam Nashwa M. A. , Abdel-Aal Ahmed M. K. , Assiri Mazen E. , Abdel-Rahim Ismail R.
Published: February 2024

Background

Purple blotch disease is a devastating disease, resulting in significant yield losses in onion. Application of synthetic fungicides is a rapid approach for the control of this disease, but extensive use of synthetic fungicides results in resistance development in pathogen. Thus, it is mandatory to explore alternative approaches to overcome the fungicide resistance challenges. The present study focused on a sustainable biocontrolling approach by using biocontrol yeast. The objective was to develop a management strategy that offers an environmentally acceptable alternative to commonly used fungicides.

Results

A total of six pathogenic isolates were obtained from the infected onion leaves, out of all tested isolates, OP-4 recorded as highly virulent with disease incidence (75.2%). Filobasidium wieringae and Pichia kluyveri drastically reduced the in vitro mycelial growth of Alternaria porri (14 and 21 mm, respectively). In the greenhouse experiment, plant inoculated with P. kluyveri suspension was the most effective, resulting in considerable reduction (77.1%) in disease severity, before two days of pathogen inoculation. However, F. wieringae showed a considerable reduction (84.5%) in disease severity when applied in combination with P. kluyveri two days post-inoculation.

Conclusions

These findings highlighted the strong biocontrol potential of P. kluyveri and F. wieringae in managing the purple blotch disease of onion and can reduce the reliance on synthetic fungicides. Further research and field trials should be conducted to optimize the application methods and evaluate the long-term effectiveness of these bioagents.
Factors predicting functional outcome after rtPA for patients with acute ischemic stroke
Authors: Hamed Yasser , Seddeek Mahrous I. , Ahmed Ali Mahmoud , Dawa Talal A. , Hashem Hasan , Othman Adel M. , Fayed Abdel-Ghaffar I. , Elbazzar Noran , Metwally Ramy A. , El Sayed Mostafa El Sayed Abd Elghany , Yousry Ahmed , Shokry Abd Elaziz
Published: February 2024

Background

Accurate outcome prediction for patients with acute ischemic stroke after intravenous recombinant tissue plasminogen activator (rtPA) treatment is essential for optimizing patients’ management. We aimed to identify factors associated with unfavorable outcomes following intravenous rtPA treatment. This study was carried out on 162 patients who presented with acute ischemic stroke within 4.5 h from onset of neurological symptoms and were eligible for intravenous rtPA. After exclusion of 48 patients, 114 patients were finally eligible for follow-up. After complete medical and neurological history, complete medical and neurological examination and brain image (CT and or MRI brain) were collected from the patients. patients eligible were included in the study. NIHS scale was assessed for all patients at time of admission, after 24 h, and follow-up for 3 months.

Results

After a 90-day follow-up period for 114 patients with acute ischemic stroke after rtPA, 35.8% had good outcome (MRS; 0–2), 18.5% had partial outcome (MRS; 3–4) and 12.5% had poor outcome (MRS; 5–6). Atrial fibrillation (AF), PH of stroke, stroke severity, and severity of symptom (NIHSS) score were significantly (P: 0.004, 0.001, 0.007 and 0.001) correlated with poor outcome after rtPA. Similarly, old age, high blood pressure at time of presentation, hypertension, and dyslipidemia were showed to carry poor outcome.

Conclusions

AF, high NIHSS score, PH of stroke, previous stroke, hypertension, dyslipidemia, and high blood pressure on presentation were significantly correlated with poor functional outcome.
Inflammation and arrhythmogenesis: a narrative review of the complex relationship
Authors: Taghdiri Andia
Published: February 2024

Background

A biological mechanism called inflammation is necessary for reacting to damaging stimuli, but it can also, ironically, play a role in the formation of arrhythmias, or the group of disorders known as arrhythmogenesis. This review delves into the intricate relationship that exists between localized and systemic inflammation and the electrophysiological changes that result in abnormal heart rhythms.

Main body

Through oxidative stress, autonomic dysfunction, electrolyte imbalances, and coagulation activation, systemic inflammation may impact arrhythmogenicity. Similar to neuropathic alterations, direct cellular damage, and structural remodeling, localized heart inflammation also predisposes to arrhythmias. Studies demonstrating the impact of cytokines on ion channel expression and function, along with clinical associations between inflammatory indicators and arrhythmia incidence, offer the molecular insights. Immune cells like macrophages that alter cardiac conduction are involved in the interaction between inflammation and electrophysiology, which further complicates the situation. Clinical ramifications include the use of anti-inflammatory drugs to treat arrhythmic episodes and the possible adjustment of arrhythmia treatment based on inflammatory condition. Even yet, further thorough study is necessary to fully understand the efficacy of these medicines.

Conclusions

Arrhythmogenesis and inflammation are inherently linked by a number of mechanisms that change the electrical characteristics of the heart. Arrhythmia treatment and prevention may benefit from therapeutic approaches that reduce inflammatory processes. The difficulties that still exist in applying this information to clinical settings highlight the necessity of continuing studies to better comprehend the subtleties of inflammation-induced electrical alterations. Progress in identifying biomarkers of inflammation and developing tailored therapies will be crucial in enhancing the prognosis of individuals suffering from arrhythmogenic disorders that are aggravated by inflammation.
Collision tumours: a meningioma and not oedema, but an oligodendroglioma
Authors: Lobo Gonçalo Gama , Alves José Luís , Novo Ana Margarida Flores , Pereira Daniela Jardim
Published: February 2024

Background

Intracranial collision tumours represent a very rare entity. We hereby report a case involving the coexistence of a meningioma and an underlying oligodendroglioma in the adjacent brain, which could be misdiagnosed as oedema if not carefully examined for atypical changes. This study aimed to shed light on the diagnostic challenges associated with intracranial collision tumours, specifically the coexistence of meningioma and oligodendroglioma.

Case presentation

A 54-year-old woman presented to the emergency department with seizures and vertigo. Brain CT revealed an expansile extra-axial left frontal lesion with calcifications and homogeneous enhancement after contrast administration, interpreted as a meningioma, with underlying vasogenic oedema. Two months later, MRI revealed a heterogeneous area in the underlying compressed brain with high intensity at T2/FLAIR sequences, initially misconceived as oedema. However, atypical features such as cortex involvement, lower ADC values (compared to vasogenic oedema), an inversion of the choline/NAA ratio, and high rCBV values led to the hypothesis of an underlying oligodendroglioma, later confirmed by histology.

Conclusions

The coexistence of histologically different tumours in the same anatomical location is extremely rare and makes the diagnosis more challenging, requiring cautious evaluation and a high suspicion from the radiologist. The look for atypical findings, described in detail in this study, and the use of additional sequences, such as spectroscopy and perfusion, might be the key to the correct diagnosis.
Seaweeds as a potential resource in diabetes management: a review
Authors: Vidyashree J. S. , Shetti Priya P. , Ghagane Shridhar C.
Published: February 2024

Background

Seaweeds are the marine macroalgae predominantly found in the coastal regions. These species have unique chemical profiles which makes them stand different from terrestrial plants. They are found to be rich in secondary metabolites which have potential in treating various unhealthy conditions. Diabetes is a chronic condition where an individual suffers from high or low sugar levels in the blood.

Main text

This review article aims to review such seaweed species that are potent in treating and managing diabetes. It has become one of the rapidly growing diseases in the world with a high occurrence rate. This paper details the mechanism of glucose regulation in the human body. Seventy percent of the total earth’s surface is accomplished by marine ecosystem. It offers home for about 25,000 species. Among them, many possess health benefits hence these are utilized directly as food or in the form of medicine.

Conclusion

In this article, various such seaweed species which have antidiabetic property has been discussed. Including edible seaweeds in daily diet have numerous healing properties. Inhibition of alpha amylase and alpha glycosidase enzyme has been associated with lowering the postprandial glucose level. This review article attempts in exploring how seaweeds and managing diabetes are interrelated.
Social Stigma and COVID-19 Vaccine Refusal in France
Authors: Peretti-Watel Patrick , Fressard Lisa , Giry Benoît , Verger Pierre , Ward Jeremy Keith
Published: February 2024

Context: In 2021, French health authorities strongly promoted vaccination against COVID-19. The authors assumed that refusing this vaccine became a stigma, and they investigated potential public stigma toward unvaccinated people among the French population.

Methods: A representative sample of the French adult population (N = 2,015) completed an online questionnaire in September 2021. The authors focused on participants who were already vaccinated against COVID-19 or intended to get vaccinated (N = 1,742). A cluster analysis was used to obtain contrasted attitudinal profiles, and the authors investigated associated factors with logistic regressions.

Findings: Regarding attitudes toward unvaccinated people, a majority of respondents supported several pejorative statements, and a significant minority also endorsed social rejection attitudes. The authors found four contrasting attitudinal profiles: moral condemnation only (32% of respondents), full stigma (26%), no stigma (26%), and stigma rejection (16%). Early vaccination, civic motives for it, faith in science, rejection of political extremes, and being aged 65 or older were the main factors associated with stigmatizing attitudes toward unvaccinated people.

Conclusions: The authors found some evidence of stigmatization toward unvaccinated people, but further research is needed, especially to investigate perceived stigmatization among them. The authors discuss their results with reference to the concept of “folk devils” and from a public health perspective.
Hierarchical processing of feature, egocentric and relational information for spatial orientation in domestic chicks
Authors: Morandi-Raikova Anastasia , Rosa-Salva Orsola , Simdianova Aleksandra , Vallortigara Giorgio , Mayer Uwe
Published: February 2024

Animals can use different types of information for navigation. Domestic chicks (Gallus gallus) prefer to use local features as a beacon over spatial relational information. However, the role of egocentric navigation strategies is less understood. Here, we tested domestic chicks' egocentric and allocentric orientation abilities in a large circular arena. In experiment 1, we investigated whether domestic chicks possess a side bias during viewpoint-dependent egocentric orientation, revealing facilitation for targets on the chicks' left side. Experiment 2 showed that local features are preferred over viewpoint-dependent egocentric information when the two conflict. Lastly, in experiment 3, we found that in a situation where there is a choice between egocentric and allocentric spatial relational information provided by free-standing objects, chicks preferentially rely on egocentric information. We conclude that chicks orient according to a hierarchy of cues, in which the use of the visual appearance of an object is the dominant strategy, followed by viewpoint-dependent egocentric information and finally by spatial relational information.