bluuebunny/crossref_metadata_2025 huggingface dataset:
Dismal outcome of refractory or relapsing patients with myelodysplasia‐related acute myeloid leukemia partially alleviated by intensive chemotherapy
Authors: Leroy Harmony , Gadaud Noémie , Bérard Emilie , Klein Emilie , Luquet Isabelle , Vial Jean‐Philippe , Rieu Jean‐Baptiste , Lechevalier Nicolas , Tavitian Suzanne , Leguay Thibaut , Largeaud Laetitia , Bidet Audrey , Delabesse Eric , Sarry Audrey , de Grande Anne‐Charlotte , Récher Christian , Pigneux Arnaud , Bertoli Sarah , Dumas Pierre‐Yves
Published: February 2024

Background

Acute myeloid leukemia (AML) with myelodysplasia‐related characteristics is a heterogeneous subset of AML that has been challenged throughout the history of myeloid malignancies classifications, considered to have similar outcomes as intermediate‐ or adverse‐risk AML depending on the subgroup. However, little is known about the fate of these patients in refractory or relapsed situation (R/R) after first line therapy.

Methods

A large series of R/R AML patients, recorded in the French DATAML registry, have received either intensive chemotherapy (ICT), azacitidine (AZA) as single agent, or best supportive care (BSC). A cohort of 183 patients (median age 63‐year‐old) with what was called at the time AML‐MRC has been explored, and data are reported here.

Results

Patient status was refractory for 93, while 90 had relapsed. Respectively, 88, 34, and 61 were included in the three treatment arms. The median OS of the whole cohort was 4.2 months (95%CI: 3.1–5.6) with a mean 1‐year overall survival of 24% ± 3.2%. There was no significant survival difference between refractory and relapsed patients. The BSC group had overall a significantly worse outcome (p = 0.0001), and this remained true in both refractory (p = 0.01) and relapsed (p = 0.002) patients. Similar survivals were observed in both groups comparing ICT and AZA.

Conclusions

These data, reporting about an ill‐explored population, indicate the poor prognosis of this condition where both ICT and AZA can be proposed. The latter, which was demonstrated here to be a feasible option, should be added to new targeted therapies.
Are embryonic stem cell markers and ALDH1A1 relevant in the context of breast cancer estrogen positivity?
Authors: Mousa Noha A. , Hussein Amal , Elemam Noha M. , Mohammed Ghada , Elwany Mona , Basha Tasneem , AlHammadi Amal A. , Majzob Rana S. , Talaat Iman M.
Published: February 2024

Background

Embryonic pluripotency markers are recognized for their role in ER− BC aggressiveness, but their significance in ER+ BC remains unclear. This study aims to investigate the prevalence of expression of pluripotency markers in ER+ BC and their effect on survival and prognostic indicators.

Methods

We analyzed data of ER+ BC patients from three large cancer datasets to assess the expression of three pluripotency markers (NANOG, SOX‐2, and OCT4), and the stem cell marker ALDH1A1. Additionally, we investigated associations between gene expression, through mRNA‐Seq analysis, and overall survival (OS). The prevalence of mutational variants within these genes was explored. Using immunohistochemistry (IHC), we examined the expression and associations with clinicopathologic prognostic indicators of the four markers in 81 ER+ BC patients.

Results

Through computational analysis, NANOG and ALDH1A1 genes were significantly upregulated in ER+ BC compared to ER‐ BC patients (p < 0.001), while POU5F1 (OCT4) was downregulated (p < 0.001). NANOG showed an adverse impact on OS whereas ALDH1A1 was associated with a highly significant improved survival in ER+ BC (p = 4.7e‐6), except for the PR− and HER2+ subgroups. Copy number alterations (CNAs) ranged from 0.4% to 1.6% in these genes, with the highest rate detected in SOX2. In the IHC study, approximately one‐third of tumors showed moderate to strong expression of each of the four markers, with 2–4 markers strongly co‐expressed in 56.8% of cases. OCT‐4 and ALDH1A1 showed a significant association with a high KI‐67 index (p = 0.009 and 0.008, respectively), while SOX2 showed a significant association with perinodal fat invasion (p = 0.017).

Conclusion

Pluripotency markers and ALDH1A1 are substantially expressed in ER+ BC tumors with different, yet significant, associations with prognostic and survival outcomes. This study suggests these markers as targets for prospective clinical validation studies of their prognostic value and their possible therapeutic roles.
Common and distinct risk factors that influence more severe and distressing shortness of breath profiles in oncology outpatients
Authors: Shin Joosun , Hammer Marilyn , Cooley Mary E. , Cooper Bruce A. , Paul Steven M. , Cartwright Frances , Kober Kord M. , Conley Yvette P. , Levine Jon D. , Miaskowski Christine
Published: February 2024

Background

Shortness of breath occurs in 10%–70% of oncology patients. Very little is known about interindividual variability in its severity and distress and associated risk factors. Using latent profile analyses (LPAs), purpose was to identify subgroups of patients with distinct severity and distress profiles for shortness of breath as single symptom dimensions. In addition, a joint LPA was done using patients' severity AND distress ratings. For each of the three LPAs, differences among the shortness of breath classes in demographic, clinical, symptom, stress, and resilience characteristics were evaluated.

Methods

Patients completed ratings of severity and distress from shortness of breath a total of six times over two cycles of chemotherapy. All of the other measures were completed at enrollment (i.e., prior to the second or third cycle of chemotherapy). Separate LPAs were done using ratings of severity and distress, as well as a joint analysis using severity AND distress ratings. Differences among the latent classes were evaluated using parametric and nonparametric tests.

Results

For severity, two classes were identified (Slight to Moderate [91.6%] and Moderate to Severe [8.4%]). For distress, two classes were identified (A Little Bit to Somewhat [83.9%] and Somewhat to Quite a Bit [16.1%]). For the joint LPA, two classes were identified (Lower Severity and Distress [79.9%] and Higher Severity and Distress [20.1%]). While distinct risk factors were associated with each of the LPAs, across the three LPAs, the common risk factors associated with membership in the worse class included: a past or current history of smoking, poorer functional status, and higher comorbidity burden. In addition, these patients had a higher symptom burden and higher levels of cancer‐specific stress.

Conclusions

Clinicians can use the information provided in this study to identify high‐risk patients and develop individualized interventions.
Prognostic factors in surgically treated tongue squamous cell carcinoma in stage T1‐2N0‐1M0: A retrospective analysis
Authors: Wang Wenxi , Wang Yuxiang , Zeng Wenhui , Xie Xubin , Li Chen , Zhou Qin , Shen Liangfang
Published: February 2024

Purpose

The study aimed to retrospectively identify the prognostic factors of surgically treated primary tongue squamous cell carcinoma (TSCC) cases and assess the benefits of surgical neck lymph node dissection (LND) in early‐stage cancer.

Methods

Patients with primary TSCC with pT1‐2N0‐1M0 stage without distant metastasis who were treated with surgery during 2014–2016 at Xiangya Hospital, Central South University were included. Univariate and multivariate Cox models were constructed to explore prognostic factors of overall survival (OS), disease‐free survival (DFS), and local recurrence‐free survival (LRFS). Sub‐group analysis was used to assess the effect of adjuvant therapy and the prognostic value of LND for the early‐stage patients.

Results

In total, 440 patients met the inclusion criteria. During the follow‐up period, the 5‐year OS, DFS, were 84.4% and 70.0%, respectively. Univariate analysis showed that TNM stage, lymphovascular invasion (LVI), and/or perineural invasion (PNI), pathological differentiation, etc. were significant predictors of OS and DFS. Multivariate analysis showed that TNM stage and the degree of pathological differentiation were independent prognostic factors for all outcomes. Besides, the number of cervical LND could independently predict both DFS and LRFS while LVI/PNI were associated with DFS. And high‐quality neck LND (≥30) significantly improved DFS and LRFS for patients of pT1cN0M0 or stage I as compared to those without LND.

Conclusions

TNM stage and pathological differentiation were crucial prognostic factors for postoperative patients with TSCC. Notably, high‐quality cervical LND was beneficial for the improvement of DFS and LRFS for patients of pT1cN0M0 or stage I.
Cocaine use and head and neck cancer risk: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium
Authors: Zhang Mingyan , Chen Chu , Li Guojun , Koric Alzina , Lee Yuan‐Chin Amy , Morgenstern Hal , Schwartz Stephen M. , Sturgis Erich M. , Boffetta Paolo , Hashibe Mia , Zhang Zuo‐Feng
Published: February 2024

Background

Cocaine is an illegal recreational drug used worldwide, yet little is known about whether cocaine inhalation (smoking/snorting) increases the risk of head and neck cancer (HNC).

Methods

The analyses were conducted by pooling data from three case–control studies with 1639 cases and 2506 controls from the International Head and Neck Cancer Epidemiology Consortium. Epidemiologic data, including cocaine use histories, were obtained in face‐to‐face interviews. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using hierarchical logistic regression models.

Results

Controlling for cumulative tobacco and alcohol use, we observed a weak positive association between cocaine use and HNC (ORever vs. never = 1.35, 95% CI: 0.96, 1.90). In stratified analysis, while we did not detect associations among never tobacco or alcohol users due to the limited sample size, the association with cocaine use was observed among tobacco users and alcohol drinkers. ORs for ever and high cumulative use (>18 times) versus never use were 1.40 (95% CI: 0.98, 2.00) and 1.66 (95% CI: 1.03, 2.69) among tobacco users, and 1.34 (95% CI: 0.93, 1.92) and 1.59 (95% CI: 1.00, 2.51) among alcohol drinkers, respectively.

Conclusion

In this pooled analysis, we observed a weak positive association between cocaine inhalation and HNC risk. Our findings provide preliminary evidence of the potential carcinogenic effect of cocaine on HNC. Because of study limitations, including limited number of cocaine users, confounding, and heterogeneity across studies, future investigations will require larger studies with more detailed information on cocaine use history.
Risk stratification of LA‐NPC during chemoradiotherapy based on clinical classification and TVRR
Authors: Tang Qianlong , Mei Chaorong , Huang Bei , Huang Rui , Kang Le , Chen Ailin , lei Na , Deng Pengcheng , Ying Shouyan , Zhang Peng , Qin Yuan
Published: February 2024

Purpose

To investigate the correlation between tumor volume reduction rate (TVRR) and prognosis in patients with diverse clinical types of nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy, thereby aptly categorizing risks and directing the personalized treatment of NPC.

Materials and Methods

A total of 605 NPC patients with varying clinical types were enrolled in this study and subsequently segregated into six subgroups based on their clinical types and TVRR. To accentuate the efficacy of grouping, Groups 1–6 underwent clustered analysis of hazard atio (HR) values pertaining to progression‐free survival (PFS), forming three risk clusters denoted as low, intermediate, and high. The log‐rank test was employed to discern differences, and R 4.1.1 was utilized for cluster analysis.

Results

According to survival rates, we classified the first (G2 and G4), second (G1 and G6), and third (G3 and G5) risk clusters as low‐, intermediate‐, and high‐risk, respectively. When comparing risk stratification with the 8th edition of the TNM staging system, our classification exhibited superior predictive prognostic performance. Subgroup analysis of treatments for each risk cluster revealed that the PFS in the neoadjuvant chemotherapy (NACT) + concurrent chemoradiotherapy (CCRT) group surpassed that of the CCRT group significantly (p < 0.05).

Conclusion

The reliance on clinical types and TVRR facilitates risk stratification of NPC during chemoradiotherapy, providing a foundation for physicians to tailor therapeutic strategies. Moreover, the risk cluster delineated for NPC patients during the mid‐term of chemoradiotherapy stands as an independent prognostic factor for progression‐free survival (PFS), overall survival (OS), distantmetastasis‐free survival (DMFS), and local recurrence‐free (LRRFS) posttreatment. Additionally, individuals in the high‐risk cluster are recommended to undergo adjuvant chemotherapy after CCRT.
Survival benefit of adjuvant chemotherapy after resection of Stage I lung adenocarcinoma containing micropapillary components
Authors: Li Ying , Zhao Junfeng , Zhao Ying , Li Ruyue , Dong Xue , Yao Xiujing , Xia Zhongshuo , Xu Yali , Li Yintao
Published: February 2024

Background

The usefulness of postoperative adjuvant chemotherapy (ACT) for patients with stage I lung adenocarcinoma with micropapillary (MIP) components remains unclear. We analyzed whether postoperative ACT could reduce recurrence in patients with stage I lung adenocarcinoma with MIP components, thereby improving their overall survival (OS) and disease‐free survival (DFS).

Methods

Data for patients with pathologically confirmed stage I lung adenocarcinoma with MIP components from January 2012 to December 2018 were retrospectively analyzed. OS and DFS were analyzed in groups and subgroups.

Results

Overall, 259 patients were enrolled. Patients who received ACT in stage IA showed significantly better survival than did those with no‐adjuvant chemotherapy (NACT); (5‐year OS 89.4% vs. 73.6%, p < 0.001; 5‐year DFS 87.2% vs. 66.0%, p = 0.008). A difference was also observed for in‐stage IB patients (5‐year OS 82.0% vs. 51.8%, p = 0.001; 5‐year DFS 76.0% vs. 41.11 %, p = 0.004). In subgroup analysis based on the proportion of MIP components, patients with 1%–5% MIP components had a significantly better prognosis in the ACT group than in the NACT group (5‐year OS 82.4% vs. 66.0%, p = 0.005; 5‐year DFS 76.5% vs. 49.1%, p = 0.032). A similar difference was observed for patients with MIP ≥5% (5‐year OS 80.7% vs. 47.8%, p = 0.009; 5‐year DFS 73.11% vs. 43.5%, p = 0.007).

Conclusion

Among patients with stage I lung adenocarcinoma with MIP components, those who received ACT showed significant survival benefits compared to those without ACT. Patients with lung adenocarcinoma with MIP components could benefit from ACT when the MIP was ≥1%.
The association of genomic alterations with PD‐L1 expression in Chinese patients with EGFR/ALK wild‐type lung adenocarcinoma and potential predictive value of Hippo pathway mutations to immunotherapy
Authors: Liu Fangfang , Zhang Xuemei , Lu Mengyao , Liu Chun , Zhang Xiaodong , Chu Qian , Chen Yuan , Zhang Peng
Published: February 2024

Background

The study focuses on PD‐L1 expression as an essential biomarker for gauging the response of EGFR/ALK wild‐type NSCLC patients to FDA‐approved immune checkpoint inhibitors (ICIs). It aims to explore clinical, molecular, and immune microenvironment characteristics associated with PD‐L1 expression in EGFR/ALK wild‐type lung adenocarcinoma patients eligible for ICI therapy.

Methods

In this retrospective study, tumor samples from 359 Chinese EGFR/ALK wild‐type lung adenocarcinoma patients underwent comprehensive evaluations for PD‐L1 expression and NGS‐targeted sequencing. The investigation encompassed the analysis and comparison of clinical traits, gene mutations, pathways, and immune signatures between two groups categorized by PD‐L1 status: negative (TPS < 1%) and positive (TPS ≥ 1%). Additionally, the study explored the link between genomic changes and outcomes following immunotherapy.

Results

High tumor mutational burden correlated significantly with PD‐L1 positivity in patients with EGFR/ALK wild‐type lung adenocarcinoma. Gene alterations, including TP53, KRAS, and others, were more pronounced in the PD‐L1 positive group. Pathway analysis highlighted higher frequencies of alterations in pathways like RTK/RAS, p53, and Hippo in PD‐L1‐positive patients. The Hippo pathway's relevance was confirmed in separate immunotherapy cohorts, associated with better outcomes. In terms of immune cell infiltration, Hippo mutants exhibited higher levels of CD68+PD‐L1+ macrophages, CD8+ T cells, and CD8+PD‐1− T cells.

Conclusions

This study offers insights into genomic features of Chinese EGFR/ALK wild‐type lung adenocarcinoma patients based on PD‐L1 expression. Notably, Hippo pathway alterations were linked to improved immunotherapy outcomes. These findings suggest connections between the Hippo pathway and PD‐L1 expression, warranting further clinical and functional investigations. The research advances our understanding of PD‐L1 expression's genomic context and immunotherapy response in EGFR/ALK wild‐type lung adenocarcinoma.
Finding a needle in a haystack: The identification of clinical practice guidelines for psychosocial oncology through an environmental scan of the academic and gray literature
Authors: Bergeron Catherine , Azzi Michelle , Coroiu Adina , Loiselle Carmen G. , Drapeau Martin , Körner Annett
Published: February 2024

Objective

Clinical practice guidelines (CPGs) are evidence‐based tools well‐suited to translate the latest research evidence into recommendations for routine clinical care. Given the rapid expansion of psychosocial oncology research, they represent a key opportunity for informing the treatment decisions of overburdened clinicians, standardizing service delivery, and improving patient‐reported outcomes. Yet, there is little consensus on how clinicians can most effectively access these tools and little to no information on the current availability and scope of CPGs for the range of psychosocial symptoms and concerns experienced by patients with cancer.

Method

Our environmental scan consisted of an academic and gray literature designed to identify currently available CPGs addressing a range of cancer‐related psychosocial symptoms.

Results

Findings revealed a total of 23 existing psychosocial oncology CPGs that met full eligibility criteria. The gray literature search was found to be more effective at identifying CPGs (n = 22) compared to the academic search (n = 9).

Conclusion

Several concerns arose from the systematic search. The limited publication of CPGs in peer‐reviewed journals may make clinicians and stakeholders more hesitant to implement CPGs due to uncertainties about the methodological rigor of the development process. Further, many existing CPGs are outdated or failed to be updated according to guideline recommendations, meaning that the recommendations may fall short of their purpose to translate up‐to‐date research findings.

Future directions

Future research should seek to systematically assess the quality of existing psychosocial oncology CPGs and shed light on the current state of implementation and adherence in clinical practice in order to better inform guideline developers on the current needs of the psychosocial oncology community.
Guidelines for outpatient administration of naxitamab: Experience from Atrium Health Levine Children's Hospital
Authors: Trovillion Erin Murphy , Michael Meghan , Jordan Cathryn C. , Brown Lauren , Phillips Katlin , Oesterheld Javier , Saulnier‐Sholler Giselle
Published: February 2024

Aim

In this publication, we will share our experience of AE management, provide guidance for appropriate staffing, and the discuss the importance of patient education when treating patients with R/R HR neuroblastoma using naxitamab.

Background

Approved treatments for patients with refractory and/or relapsed (R/R) high‐risk (HR) neuroblastoma are limited, and there is a high unmet need for new treatment combinations. Naxitamab is a disialoganglioside 2 (GD2)‐binding antibody that was approved by the United States Food and Drug Administration in 2020 for use in combination with granulocyte–macrophage colony‐stimulating factor for the treatment of patients with R/R HR neuroblastoma in the bone and/or bone marrow and who have demonstrated a partial response, minor response, or stable disease with prior therapy.

Methods

The pediatric oncology team at Atrium Health Levine Children’s Hospital has successfully treated several patients with naxitamab both alone and in combination with chemotherapy, with no patients requiring unplanned overnight hospitalization and few severe adverse events (AEs). To accomplish this, the team at Levine Children’s Hospital established standard operating procedures for naxitamab, a therapy defined as high acuity due to the potential for acute AEs with rapid onset and that benefits from continuous monitoring by a nursing team and a dedicated provider.

Conclusions

This will provide a practical guide for institutions offering naxitamab to their patients, and ensure successful administration of this high acuity treatment in the outpatient setting.
2,5‐Thienylene‐Strapped [26]Hexaphyrin as Multifunctional Chemosensor for Hg2+, Cu2+, and F− Ions
Authors: Kerayu Bulti Abdisa , Hung Chen‐Hsiung , Vardhaman Anil Kumar , Ayanie Tibebu Alemu , Geneti Busha Jima
Published: February 2024

The sensing behavior of 2,5‐thienylene‐bridged tetrakis(2,6‐dichlorophenyl)‐[26]hexaphyrin (2) towards various metal ions and anions were investigated by UV–vis and fluorescence spectroscopies. Using this strapped hexaphyrin (2), the molecular sensor displayed highly selective and sensitive colorimetric responses to Cu2+ and Hg2+ in MeOH/THF. The spectral changes are distinctive enough in the visible region of the spectrum to enable naked‐eye detection. The detection limits of Cu2+ and Hg2+ using this chemo‐sensor in a mixed MeOH/THF solution were 1.978 and 1.283 μM, respectively, and 1.052 μM for F− in dichloromethane. Chemosensor 2,5‐thienylene strapped [26]hexaphyrin (2) shows absorption responses both a 1 : 1 molecular ratio for 2 interacting with Cu2+ and Hg2+ and a 1 : 2 ratio between 2 and F− ions.
Curcumin – Bioavailability Enhancement by Prodrug Approach and Novel Formulations
Authors: Chelimela Narsaiah , Alavala Rajasekhar Reddy , Satla Shobha Rani
Published: February 2024

Curcumin is a diverse natural pharmacological agent involved in various signal transduction mechanisms. Therapeutically, this potent molecule faces different challenges and issues related to low bioavailability due to its poor aqueous solubility, less permeability, faster elimination and clearance. Experts in synthetic chemistry and pharmaceuticals are continuously sparing their efforts to overcome these pharmacokinetic challenges by using different structural modification strategies and developing novel drug delivery systems. In this mini‐review article, we are focusing on development of curcumin derivatives by different possible routes like conjugation with biomolecules, natural polymers, synthetic polymers, natural products, metal conjugates and co‐ administration with natural metabolic inhibitors. In addition to that, it was also focused on the preparation of modified formulations such as micelles, microemulsions, liposomes, complexes with phospholipids, micro and nanoemulsions, solid lipid nanoparticles, nano lipid carriers, biopolymer nanoparticles and microgels to improve the pharmacokinetic properties of the curcumin without altering its pharmacodynamics activity. This review helps to understand the problems associated with curcumin and different strategies to improve its pharmacokinetic profile.
Acetylated oligopeptide and N‐acetylcysteine protect against iron overload‐induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2/HO‐1 and downregulation of MMP‐9/TIMP‐1 and GFAP
Authors: Kamel Amira A. , Nassar Ahmed Y. , Meligy Fatma Y. , Omar Yomna A. , Nassar Gamal A. Y. , Ezzat Ghada M.
Published: February 2024

Iron accumulation in the brain causes oxidative stress, blood–brain barrier (BBB) breakdown, and neurodegeneration. We examined the preventive effects of acetylated oligopeptides (AOP) from whey protein on iron‐induced hippocampal damage compared to N‐acetyl cysteine (NAC). This 5‐week study used 40 male albino rats. At the start, all rats received 150 mg/kg/day of oral NAC for a week. The 40 animals were then randomly divided into four groups: Group I (control) received a normal diet; Group II (iron overload) received 60 mg/kg/day intraperitoneal iron dextran 5 days a week for 4 weeks; Group III (NAC group) received 150 mg/kg/day NAC and iron dextran; and Group IV (AOP group) received 150 mg/kg/day AOP and iron dextran. Enzyme‐linked immunosorbent assay, spectrophotometry, and qRT‐PCR were used to measure MMP‐9, tissue inhibitor metalloproteinase‐1 (TIMP‐1), MDA, reduced glutathione (GSH) levels, and nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1) gene expression. Histopathological and immunohistochemical detection of nestin, claudin, caspase, and GFAP was also done. MMP‐9, TIMP‐1, MDA, caspase, and GFAP rose in the iron overload group, while GSH, Nrf2, HO‐1, nestin, and claudin decreased. The NAC and AOP administrations improved iron overload‐induced biochemical and histological alterations. We found that AOP and NAC can protect the brain hippocampus from iron overload, improve BBB disruption, and provide neuroprotection with mostly no significant difference from healthy controls.
Bacterial Glycolipid Acting on Protein Transport Across Membranes
Authors: Mori Shoko , Shionyu Masafumi , Shimamoto Keiko , Nomura Kaoru
Published: February 2024

The process of protein transport across membranes involves a variety of factors and has been extensively investigated. Traditionally, proteinaceous translocons and chaperones have been recognized as crucial factors in this process. However, recent studies have highlighted the significant roles played by lipids and a glycolipid present in biological membranes in membrane protein transport. Membrane lipids can influence transport efficiency by altering the physicochemical properties of membranes. Notably, our studies have revealed that diacylglycerol (DAG) attenuates mobility in the membrane core region, leading to a dramatic suppression of membrane protein integration. Conversely, a glycolipid in Escherichia coli inner membranes, named membrane protein integrase (MPIase), enhances integration not only through the alteration of membrane properties but also via direct interactions with membrane proteins. This review explores the mechanisms of membrane protein integration mediated by membrane lipids, specifically DAG, and MPIase. Our results, along with the employed physicochemical analysis methods such as fluorescence measurements, nuclear magnetic resonance, surface plasmon resonance, and docking simulation, are presented to elucidate these mechanisms.
NR1H4 mutation and rapid progressive intrahepatic cholestasis in infancy: A case report and literature review
Authors: Yang Chiao‐Yu , Tsai Hung‐Wen , Chou Yen‐Yin , Yang Yao‐Jong
Published: February 2024

Farnesoid X receptor (FXR) is a nuclear bile acid receptor encoded by the NR1H4 gene, a vital regulator of bile acid homeostasis. Pathogenic mutations of NR1H4 manifest as low gamma‐glutamyl transferase (GGT) cholestasis with rapid progression to liver failure, which is referred to as progressive familial intrahepatic cholestasis 5 (PFIC‐5). Herein, we present a case with rapid progressive cholestasis, liver failure in early infancy with the NR1H4 termination mutation.
Primary Sjogren's syndrome presenting as ptosis and eyelid swelling: A case report
Authors: Khan Alishba Ashraf , Mumtaz Shamaila , Malik Javeria , Manzoor Muhammad Shahzad , Maqbool Faran , Shafique Mudassir , Nazir Maheen , Ibn‐e‐Shad Zohad , Kandel Kamal
Published: February 2024

Key Clinical Message

This unique case report of primary Sjogren's syndrome (pSS) shows bilateral ptosis and significant periorbital edema, compromising vision. To avoid misleading diagnosis, antibody tests must be evaluated and interpreted in the context of clinical findings.

Primary Sjögren's syndrome is an idiopathic, autoimmune disorder involving the lacrimal and salivary glands characterized by both localized and systemic manifestations including xerostomia and keratoconjunctivitis sicca. Myasthenia Gravis (MG) is also an autoimmune disorder characterized by the development of auto‐antibodies against nicotinic acetylcholine receptors that causes decreased muscle response to stimulation. It usually presents with ptosis and generalized body weakness. Ophthalmological involvement is common in both disorders but ptosis is very rarely seen in pSS. We report the case of a 27‐year‐old woman presenting to our clinic with the complaint of ptosis and eyelid swelling. She also had a positive anti‐acetylcholine receptor antibody test and her initial presentation mimicked Myasthenia Gravis. Her autoimmune workup revealed a positive titer of Anti Ro SSA antibodies. Myasthenia Gravis was ruled out on electrodiagnostic studies which showed no decremental response, and pSS was confirmed on lip biopsy. Our case highlights that it is important to interpret the antibody test results in the context of clinical findings as we can have spurious results in autoimmune diseases. Autoimmune conditions can have varying presenting complaints hence, clinical judgment should always overrule diagnostic investigations and should thus guide patient management.
Small Molecule‐Drug Conjugates: Opportunities for the Development of Targeted Anticancer Drugs
Authors: Zhang Jingjing , Hu Fanchun , Aras Omer , Chai Yichao , An Feifei
Published: February 2024

Conventional chemotherapy is insufficient for precise cancer treatment due to its lack of selectivity and inevitable side effects. Targeted drugs have emerged as a promising solution for precise cancer treatment. A common strategy is to conjugate therapeutic agents with ligands that can specifically bind to tumor cells, providing targeted therapy. Similar to the more successful antibody drug conjugates (ADCs), small molecule drug conjugates (SMDCs) are another promising class of targeted drugs, consisting of three parts: targeting ligand, cleavable linker and payload. Compared to ADCs, SMDCs have the advantages of smaller size, better permeability, simpler preparation process and non‐immunogenicity, making them a promising alternative to ADCs. This review describes the characteristics of the targeting ligand, linker and payload of SMDCs and the criteria for selecting a suitable one. We also discuss recently reported SMDCs and list some successful SMDCs that have entered clinical trials.
First person profile: Betty Ferrell, PhD, RN
Authors: Nierengarten Mary Beth
Published: February 2024

This news section offers Cancer readers timely information on events, public policy analysis, topical issues, and personalities. In this issue, Betty Ferrell, PhD, RN, reflects on her career, built on a belief that palliative care should be offered from the beginning of a cancer diagnosis rather than only as an end‐of‐life therapy. In addition, capivasertib with fulvestrant is now available in the United States for select patients with advanced breast cancer for whom previous treatments have failed, and the Food and Drug Administration has granted marketing authorization for the Invitae Common Hereditary Cancers Panel.
Reappraisal of prognostic factors used in the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 study for localized rhabdomyosarcoma to optimize risk stratification and generate a prognostic nomogram
Authors: De Salvo Gian Luca , Del Bianco Paola , Minard‐Colin Veronique , Chisholm Julia , Jenney Meriel , Guillen Gabriela , Devalck Christine , Van Rijn Rick , Shipley Janet , Orbach Daniel , Kelsey Anna , Rogers Timothy , Guerin Florent , Scarzello Giovanni , Ferrari Andrea , Cesen Mazic Maja , Merks Johannes H. M. , Bisogno Gianni ,   for the European Pediatric Soft Tissue Sarcoma Study Group
Published: February 2024

Background

The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event‐free survival and provide a rationale for risk stratification in future trials.

Methods

The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005‐000217‐35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second‐order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5‐year event‐free survival (EFS) probabilities.

Results

The EFS and overall survival rates at 5 years were 70.9% (95% confidence interval, 68.6%–73.1%) and 81.0% (95% confidence interval, 78.9%–82.8%), respectively. The multivariable model retained five prognostic factors, including age at diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5‐year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low‐risk, intermediate‐risk, high‐risk, and very‐high‐risk groups, respectively, and the corresponding 5‐year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively.

Conclusions

The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.
Physiologically Based Pharmacokinetic Absorption Model for Pexidartinib to Evaluate the Impact of Meal Contents and Intake Timing on Drug Exposure
Authors: Nakayama Shintaro , Lukacova Viera , Tanabe Shuichi , Watanabe Akiko , Mullin Jim , Suarez‐Sharp Sandra , Shimizu Takako
Published: February 2024

Pexidartinib is a systemic treatment for patients with tenosynovial giant cell tumor not amenable to surgery. Oral absorption of pexidartinib is affected by food; administration with a high‐fat meal (HFM) or low‐fat meal (LFM) increases absorption by approximately 100% and approximately 60%, respectively, compared with the fasted state. Pexidartinib is currently dosed 250 mg orally twice daily with an LFM (approximately 11‐14 g of total fat). We developed a physiologically based pharmacokinetic model to determine the impact on drug exposure of dose timing with respect to meals, meal type, and caloric content. A 15%‐16% increase in plasma exposure was predicted when consuming an HFM 1 hour after dosing with an LFM, but almost no effect on pharmacokinetics was predicted when an HFM was consumed 3 hours or more before or after pexidartinib dosing with an LFM. Exposure was not significantly affected when pexidartinib was taken with a 500‐kcal LFM over the range of fat (approximately 11‐14 g of total fat; 20%‐25% calories from fat) for an LFM. These findings on timing of pexidartinib dose with respect to meals should be considered by patients and physicians to reduce the potential for side effects.
Production and cultivation dynamics of millets in India
Authors: Yadav O. P. , Singh D. V. , Kumari Vandita , Prasad Manoj , Seni Sushmita , Singh Roshan Kumar , Sood S. , Kant Lakshmi , Rao B. Dayakar , Madhusudhana R. , Bhat B. Venkatesh , Gupta S. K. , Yadava D. K. , Mohapatra T.
Published: February 2024

Millets gained a great attention at the global level in 2023 which is celebrated as the “International Year of Millets” to create awareness to eventually promote consumption and production. An attempt is made here to understand the cultivation and production dynamics of millets as influenced by their demand and supply. We also assess challenges and emerging opportunities to make millets more productive, competitive, and relevant to future farming. Millets registered a 60% decline in area and a 200% rise in productivity, but production has remained the same during the last seven decades. The demand of millets decreased as food due to greater incentives (purchasing grain at a pre‐determined price) and policies (distribution of grains to the public at a subsidized rate) in favor of wheat and rice. Millets would play a greater role in future agriculture due to challenges posed by climate change, limited water supply, and reduced agro‐biodiversity. This would need a much greater intensity of investment in millet research and adequate support as extended to wheat and rice. Increased emphasis on their genetic improvement and agronomic management is required to develop cultivars, using new tools and technologies, with high production potential and adequate environmental adaptation to make millets competitive with other crops. Mainstreaming the nutritional traits in millet breeding is also critically important to develop high‐yielding cultivars with improved grain quality traits. Promoting millet consumption would remain the key issue for increasing their demand as food, feed, and industrial raw materials through policies and awareness programs. Strengthening of value chain will help in diversifying agri‐food production system and creating an ecosystem for millet promotion.
Deubiquitination of Abelson tyrosine kinase: A novel regulatory mechanism targeting non‐small cell lung cancer glycolysis
Authors: Yu Tong , Jiang Shuxia , Shan Hongli
Published: February 2024

In this commentary, we briefly introduce the importance of metabolic reprogramming in non‐small celllung cancer (NSCLC) and the role of aberrant glycolysis processes intumorigenesis and metastasis. We further summarize the regulation of deubiquitylation modification on glycolysis‐related kinases in this system. Andwe discusse the major discovery the research by He Yuanming et al. published in Clinical and Translational Medicine.Their study demonstrates targeting the USP7‐c‐Abl‐HK2 axis represents a promising therapeutic strategt for NSCLC.
Gastrointestinal stromal tumors in fine‐needle aspiration biopsies
Authors: Mousavi Seyedreza , Ono Yuho , VanderLaan Paul A. , Guzmán‐Arocho Yaileen D.
Published: February 2024

Gastrointestinal stromal tumors (GISTs), although rare, are the most common mesenchymal neoplasms of the gastrointestinal tract. Their potential for malignancy underscores the significance of identifying them through cytomorphologic findings and pertinent immunohistochemical markers. GISTs can emerge anywhere along the gastrointestinal tract with a predilection for the stomach. The clinical manifestations vary from nonspecific abdominal symptoms to incidental discovery during diagnostic interventions for unrelated signs and symptoms. Cytologically, GIST aspirates contain spindle or epithelioid cells with immunoreactivity for CD117/c‐KIT, DOG‐1, and CD34. Molecularly, KIT or PDGFRA mutations are prevalent, guiding targeted therapy with tyrosine kinase inhibitors. Distinct subtypes like succinate dehydrogenase‐deficient GISTs pose challenges, often affecting younger individuals and displaying unique features. Histologically, GISTs are graded by mitotic rates, aiding prognostication. Distinguishing GISTs from similar entities is pivotal, necessitating attention to their immunostaining patterns for making an accurate diagnosis and molecular alterations for effectively planning treatment. Common differential diagnoses include leiomyoma, schwannoma, and solitary fibrous tumor. This article presents a classic GIST case and showcases relatively simple diagnostic clues for identifying similar lesions that may occur in diverse locations.
The thermal breadth of temperate and tropical freshwater insects supports the climate variability hypothesis
Authors: Dewenter Beatrice S. , Shah Alisha A. , Hughes Jane , Poff N. LeRoy , Thompson Ross , Kefford Ben J.
Published: February 2024

Climate change involves increases in mean temperature and changes in temperature variability at multiple temporal scales but research rarely considers these temporal scales. The climate variability hypothesis (CVH) provides a conceptual framework for exploring the potential effects of annual scale thermal variability across climatic zones. The CVH predicts ectotherms in temperate regions tolerate a wider range of temperatures than those in tropical regions in response to greater annual variability in temperate regions. However, various other aspects of thermal regimes (e.g. diel variability), organisms' size and taxonomic identity are also hypothesised to influence thermal tolerance. Indeed, high temperatures in the tropics have been proposed as constraining organisms' ability to tolerate a wide range of temperatures, implying that high annual maximum temperatures would be associated with tolerating a narrow range of temperatures. We measured thermal regimes and critical thermal limits (CTmax and CTmin) of freshwater insects in the orders Ephemeroptera (mayflies), Plecoptera (stoneflies) and Trichoptera (caddisflies) along elevation gradients in streams in temperate and tropical regions of eastern Australia and tested the CVH by determining which variables were most correlated with thermal breadth (Tbr = CTmax − CTmin). Consistent with the CVH, Tbr tended to increase with increasing annual temperature range. Tbr also increased with body size and Tbr was generally wider in Plecoptera than in Ephemeroptera or Trichoptera. We also find some support for a related hypothesis, the climate extreme hypothesis (CEH), particularly for predicting upper thermal limits. We found no evidence that higher annual maximum temperature constrained individuals' abilities to tolerate a wide range of temperatures. The support for the CVH we document suggests that temperate organisms may be able to tolerate wider ranges of temperatures than tropical organisms. There is an urgent need to investigate other aspects of thermal regimes, such as diel temperature cycling and minimum temperature.
Migratory singers dynamically overlap the signal space of a breeding warbler community
Authors: Sblendorio Joanna M. , Vonhof Maarten J. , Gill Sharon A.
Published: February 2024

Migratory species inhabit many communities along their migratory routes. Across taxa, these species repeatedly move into and out of communities, interacting with each other and locally breeding species and competing for resources and niche space. However, their influence is rarely considered in analyses of ecological processes within the communities they temporarily occupy. Here, we explore the impact of migratory species on a breeding community using the framework of acoustic signal space, a limited resource in which sounds of species within communities co‐exist. Migrating New World warblers (Parulidae, hereafter referred to as migrant species) often sing during refueling stops in areas and at times during which locally breeding warbler species (hereafter breeding species) are singing to establish territories and attract mates. We used eBird data to determine the co‐occurrence of 19 migrant and 11 breeding warbler species across spring migration in SW Michigan, generated a signal space from song recordings of these species, and examined patterns of signaling overlap experienced by breeding species as migrants moved through the community. Migrant species were present for two‐thirds of the breeding season of local species, including periods when breeding species established territories and attracted mates. Signaling niche overlap experienced by individual breeding species was idiosyncratic and varied over time, yet niche overlap between migrant and breeding species occurred more commonly than between breeding species or between migrant species. Nevertheless, the proportion of niche overlap between migrant and breeding warblers was similar to overlap among breeding species. Our findings showed that singing by migrant species overlapped the signals of many breeding species, suggesting that migrants could have unexplored impacts on communication in breeding species, potentially affecting song detection and song evolution. Our study contributes to a growing body of research documenting the impacts of migratory species on communities and ecosystems.
Early warning indicators capture catastrophic transitions driven by explicit rates of environmental change
Authors: Arumugam Ramesh , Guichard Frederic , Lutscher Frithjof
Published: February 2024

In response to external changes, ecosystems can undergo catastrophic transitions. Early warning indicators aim to predict such transitions based on the phenomenon of critical slowing down at bifurcation points found under a constant environment. When an explicit rate of environmental change is considered, catastrophic transitions can become distinct phenomena from bifurcations, and result from a delayed response to noncatastrophic bifurcations. We use a trophic metacommunity model where transitions in time series and bifurcations of the system are distinct phenomena. We calculate early warning indicators from the time series of the continually changing system and show that they predict not the bifurcation of the underlying system but the actual catastrophic transition driven by the explicit rate of change. Predictions based on the bifurcation structure could miss catastrophic transitions that can still be captured by early warning signals calculated from time series. Our results expand the repertoire of mechanistic models used to anticipate catastrophic transitions to nonequilibrium ecological systems exposed to a constant rate of environmental change.
Upregulation of IL4‐induced gene 1 enzyme by B2 cells during melanoma progression impairs their antitumor properties
Authors: Bekkat Fériel , Seradj Malvina , Lengagne Renée , Fiore Frédéric , Kato Masashi , Lucas Bruno , Castellano Flavia , Molinier‐Frenkel Valérie , Richard Yolande , Prévost‐Blondel Armelle
Published: February 2024

B cells present in human cutaneous melanoma have been associated with protective or detrimental effects on disease progression according to their phenotype. By using the RET model of spontaneous melanoma and adoptive transfer of B16 melanoma cells, we show that immature and follicular B2 (B2‐FO) cells exert a protective effect on melanoma progression by promoting the generation of effector memory T cells and limiting the recruitment of polymorphonuclear myeloid‐derived suppressor cells. Unfortunately, this beneficial effect progressively wanes as a consequence of enhanced expression of the IL4‐induced gene 1 (IL4I1) enzyme by immature B cells and B2‐FO cells. Endogenous IL4I1 selectively decreases CXCR5 expression in splenic immature B cells, subverting their trafficking to primary tumors and enhancing the production of IL‐10 by B2 cells, thereby promoting an immunosuppressive microenvironment. Accordingly, B2 cells from RET IL4I1KO mice more efficiently controlled B16 melanoma growth than B2 cells from IL4I1‐competent RET mice. Collectively, immature B cells and B2‐FO cells are key actors in the control of melanoma growth, but their mobility and functions are differently impaired by IL4I1 overexpression during melanoma progression. Thus, our present data strongly urge us to associate an IL4I1 antagonist with current immunotherapy to improve the treatment of metastatic melanoma.