bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and validation of a novel senescence-related biomarker for thyroid cancer to predict the prognosis and immunotherapy
Authors: Guo Yangyang , Cen Kenan , Chen Qiaoqiao , Dai Ying , Mai Yifeng , Hong Kai
Published: January 2023

Introduction

Cellular senescence is a hallmark of tumors and has potential for cancer therapy. Cellular senescence of tumor cells plays a role in tumor progression, and patient prognosis is related to the tumor microenvironment (TME). This study aimed to explore the predictive value of senescence-related genes in thyroid cancer (THCA) and their relationship with the TME.

Methods

Senescence-related genes were identified from the Molecular Signatures Database and used to conduct consensus clustering across TCGA-THCA. Differentially expressed genes (DEGs) were identified between the clusters used to perform multivariate Cox regression and least absolute shrinkage and selection operator regression (LASSO) analyses to construct a senescence-related signature. TCGA dataset was randomly divided into training and test datasets to verify the prognostic ability of the signature. Subsequently, the immune cell infiltration pattern, immunotherapy response, and drug sensitivity of the two subtypes were analyzed. Finally, the expression of signature genes was detected across TCGA-THCA and GSE33630 datasets, and further validated by RT-qPCR.

Results

Three senescence clusters were identified based on the expression of 432 senescence-related genes. Then, 23 prognostic DEGs were identified in TCGA dataset. The signature, composed of six genes, showed a significant relationship with survival, immune cell infiltration, clinical characteristics, immune checkpoints, immunotherapy response, and drug sensitivity. Low-risk THCA shows a better prognosis and higher immunotherapy response than high-risk THCA. A nomogram with perfect stability constructed using signature and clinical characteristics can predict the survival of each patient. The validation part demonstrated that ADAMTSL4, DOCK6, FAM111B, and SEMA6B were expressed at higher levels in the tumor tissue, whereas lower expression of MRPS10 and PSMB7 was observed.

Discussion

In conclusion, the senescence-related signature is a promising biomarker for predicting the outcome of THCA and has the potential to guide immunotherapy.
Marine environmental pollution and offshore aquaculture structure: Evidence from China
Authors: Yuan Bin , Cui Yuhu , An Dong , Jia Zhaoxin , Ding Wenyan , Yang Lin
Published: January 2023

The marine environment pollution is becoming an important factor that restricts the sustainable development of mariculture in China. This study takes 10 Chinese coastal provinces (cities) as the study area, based on the rationalization and upgrading dimensions of industrial structure, and innovatively constructs an analytical framework of marine environmental pollution and offshore aquaculture structure to identify the intrinsic relationship between them; and introduces a spatial econometric model to alleviate the estimation bias caused by the public goods attribute of marine environment and improve the reliability of research conclusions. The results show that: (1) The rationalization of the offshore aquaculture structure in China is relatively weak, showing a “concentrated and contiguous” distribution pattern towards the developed aquaculture areas; at the same time, but the differences between regions are expanding; (2) The rationalization and upgrading of the offshore aquaculture structure are affected by the pollution of the marine environment. The degree of upgrading shows different trends; (3) There is a significant spatial adjacency and threshold effect of the negative impact of marine environmental pollution on offshore farming structure. However, due to the limitations of data, the accuracy of our data and the effectiveness of the measurement of industrial structure indicators still need to be improved. Therefore, governmental departments should consider the development of the surrounding areas as well as the pollution emission in the region, and jointly promote the optimization and adjustment of China’s offshore aquaculture structure through the construction of a coordinated management mechanism of marine pollution prevention and treatment.
Generation of macro-vortices in estuarine compound channels
Authors: He Chang , Yin Zhen-Yu , Stocchino Alessandro , Wai Onyx Wing Hong
Published: January 2023

We report the results of a numerical investigation of the flow structure and mechanism of macro-vortex generation in estuarine compound channels. The Finite-Volume Coastal Ocean Model (FVCOM) was implemented to simulate tidal currents in compound channels, e.g., the Lantau Channel, which lies in the middle of the Pearl River Estuary (PRE). Results showed that the velocity magnitude in channels was significantly larger than that of floodplains during the ebb and flood phases, resulting in a high-velocity gradient at the depth discontinuity. Vorticity and Q-criterion were used to analyze the macro-vortex distribution inside the PRE. Massive macro-vortices were generated along the compound channels where high vorticity was also detected. The across-estuary sections with single and multiple channels were selected as representatives to analyze velocity distribution during ebb and flood tides. To characterize the channel flow, the ratio of the main channel depth of the Lantau Channel to floodplain depth (Rh) was calculated using the topography information and surface elevation of sections. It was found that there existed a channel segment where the flow periodically changed between shallow flow (Rh > 3) and intermediate flow (2< Rh< 3). This dynamic change in Rh greatly influenced the generation of macro-vortices. Transverse dispersive stresses were calculated to evaluate the longitudinal momentum transfer in the lateral direction. We found that the dispersive stresses could play an important role in the redistribution of momentum in addition to barotropic and baroclinic transport. This paper revealed the mechanism of the dynamic generation of macro-vortices in the estuarine compound channel, serving as a valuable example in understanding natural compound channel flows.
Numerical study on the internal fluid mixing and its influencing mechanisms of the wave-driven floating photobioreactor for microalgae production
Authors: Zhao Yunpeng , Jia Guangchen , Cheng Yuan , Zhu Hongyu , Chi Zhanyou , Shen Haibin , Zhu Chenba
Published: January 2023

The wave-driven floating photobioreactors (PBRs) with advantages of easy in scaling-up, low energy inputs and low fabricating cost, hold great potential for massive and cost-energy effective microalgae production. However, their applications may be seriously challenged by intermittent waves that could produce very poor mixing under poor wave conditions, leading to a significant reduction of biomass productivity or even collapse of the cultures. To improve the utilization efficiency of waves for efficient and stable microalgae production in the floating PBRs, this work aims at numerically studying the fluid-dynamics of the floating PBRs, as well as the effects from wave conditions, culture depth and three different PBRs’ structures of square, rectangular and circular types. The results showed that the liquid inside the floating PBRs follow a periodic sinusoidal and reciprocating flow, and the square PBR had aggressive mixing characteristics at high wave excitation frequency, while the rectangular PBR produced more intense mixing at low wave excitation frequency. Regarding the culture depth, the dependence of liquid mixing on the culture depth showed a decreasing trend. Moreover, the results indicated that the PBRs with a high culture depth had several dead zones, although there was apparent upward flow at the high excitation frequency. This work provides valuable insight into increasing the utilization efficiency of wave energy for mixing enhancement in the floating PBRs and their design.
Effect of ultrasonic vibration on residual stress in plasma cladding of iron-based alloy
Authors: Lai Youbin , Yue Wenwen , Zhang Yichuan
Published: January 2023

To explore the effect of ultrasonic vibration power and frequency on the residual stress of single-channel iron-based alloy plasma cladding, the single-factor ultrasonic vibration plasma cladding test was designed, and ten groups of single-channel iron-based alloy cladding samples under different process parameters were studied. The drilling method was used to measure the residual stress of the substrate at the beginning, middle and tail positions of each sample cladding layer. The residual stress of the substrate was analyzed and the significant characteristics of the effect of ultrasonic vibration power and frequency on the residual stress at different positions were explored using variance analysis. The results show that the residual stress is significantly reduced after applying ultrasonic waves. When the ultrasonic frequency is constant and the ultrasonic power is 240 W, the residual stress of the formed sample is the smallest. Compared with the unapplied ultrasonic assistance, the residual stress in the X direction is reduced by 62.56%, and the residual stress in the Y direction is reduced by 63.23%. When the ultrasonic power is constant and the ultrasonic frequency is 28 kHz, the residual stress of the formed sample is the smallest. Compared with the unapplied ultrasonic assistance, the residual stress in the X direction is reduced by 17.23%, and the residual stress in the Y direction is reduced by 19.79%. The ultrasonic power significantly affects the middle part of the substrate, and the ultrasonic frequency significantly affects each point of the substrate.
Uveal melanoma incidence trends in Canada: 1992–2010 vs. 2011–2017
Authors: Conte Santina , Lagacé François , Ghazawi Feras M. , Cattelan Leila , Nath Siddharth , Dhillon Jobanpreet , Nedjar Hacene , Rahme Elham , Sasseville Denis , Burnier Miguel N. , Litvinov Ivan V.
Published: January 2023

Background/aims

Uveal melanoma is the most common type of non-cutaneous melanoma and the most common ocular malignancy in the adult population, especially affecting Caucasians (98% of cases). Despite its low incidence rate, we have noted increasing incidence trends in recent years.

Methods

We analyzed uveal melanoma incidence data using the Canadian Cancer Registry (CCR) for 2011–2017 years. The data was examined using the International Classification of Diseases for Oncology, Third Edition, codes for all uveal melanoma subtypes. The data for 2011–2017 was then compared to previously published work by our research group for uveal melanoma incidence in Canada between 1992 and 2010 using the same methodology.

Results

Between 2011 and 2017, 1,215 patients were diagnosed with uveal melanoma, 49% of whom were females. The percentage distribution of uveal melanoma between the sexes was similar between 1992–2010 and 2011–2017, whereby of the 2,215 diagnoses of uveal melanoma in 1992–2010, 47.9% were females. The change in the incidence rate for this cancer has doubled between 1992–2010 and 2011–2017, from 0.074 to 0.15 cases per million individuals per year. Our study documents that the Canadian 2011–2017 age-standardized incidence rate (ASIR) for uveal melanoma against the World Health Organization (WHO) 2000–2025 world population standard was 5.09 cases per million individuals per year (95% confidence interval, 4.73–5.44), as compared with the 1992–2010 rate of 3.34 cases per million individuals per year (95% confidence interval, CI 3.20 to 3.47).

Conclusion

This work demonstrates an ongoing, steady increase in uveal melanoma incidence in Canada in recent years.
Scanning and three-dimensional-printing using computed tomography of the “Golden Boy” mummy
Authors: Saleem Sahar N. , Seddik Sabah Abd el-Razek , el-Halwagy Mahmoud
Published: January 2023

Ancient Egyptian mummies represent an opportunity to learn more about the health, beliefs, and skills of humans in antiquity. A fully wrapped mummy, from a Late Ptolemaic cemetery (c.332-30 BC) in Edfu, Egypt, has been stored, unexamined, at the Cairo Egyptian Museum since 1916. We hypothesized that scanning and 3D-printing the mummy using Computed Tomography (CT) could help in documenting and promoting its public display. CT enabled non-invasive digital unwrapping and revealed a well-preserved mummy. Biological sex could be determined from the presence of male genitalia; epiphyseal fusion and tooth eruption indicated an approximate age at death of 14–15 years. The deceased had healthy teeth and bones without evidence of poor nutrition or disease. CT detected a high-quality mummification process that included brain removal through an iatrogenic defect of the cribriform plate and viscera removal via a left lower-abdominal incision. The heart remained in the chest as a spiritual symbol. Resin was poured into the emptied cranial and torso cavities, and linen packs were placed inside the torso. The Mummy’s external ornamentation includes a gilded head mask, a pectoral cartonnage, and a pair of sandals. CT identified 49 amulets inside the mummy and between the wrappings, arranged in three columns. The amulets have 21 different shapes, including Udjat, scarabs, Ajet, Djed-pillar, Tyt, Placenta, Double-Plume, and Right-angle. CT densities indicated that 30 (61%) amulets were metal (likely gold), and the other amulets were made of faience, stones, or fired clay. The embalmers placed amulets to protect and provide vitality for the body for the afterlife. A gold tongue amulet was placed inside the mouth to ensure the deceased could speak in the afterlife. A Two-finger amulet was placed beside the penis to protect the embalming incision. 3D-printing enabled the tactile and visual study of a heart scarab found inside the thoracic cavity. Findings from this study suggest that ancient Egyptians valued their children and provided them with ritual treatment. State-of-the-art techniques such as CT and 3D printing provided valuable insights and supported the museum display of the mummy, nicknamed “The Golden Boy.”
Effects of maternal characteristics and medical history on first trimester biomarkers for preeclampsia
Authors: Torres-Torres Johnatan , Espino-y-Sosa Salvador , Villafan-Bernal Jose Rafael , Orozco-Guzman Luis Enrique , Solis-Paredes Juan Mario , Estrada-Gutierrez Guadalupe , Martinez-Cisneros Romeo Adalid , Mateu-Rogell Paloma , Acevedo-Gallegos Sandra , Martinez-Portilla Raigam Jafet
Published: January 2023

Objective

To identify and quantify the effects of maternal characteristics and medical history on the distribution of Placental Growth Factor (PlGF), mean arterial pressure (MAP), and Uterine Artery Mean Pulsatility Index (UtA-PI); and to standardize the expected values for these biomarkers in the first trimester to create unique multiples of the median (MoMs) for Latin-American population.

Methods

This is a prospective cohort built exclusively for research purposes of consecutive pregnant women attending their first-trimester screening ultrasound at a primary care center for the general population in Mexico City between April 2019 and October 2021. We excluded fetuses with chromosomal abnormalities, major fetal malformations, and women delivering in another care center. Linear regression was used on log-transformed biomarkers to assess the influence of maternal characteristics on non-preeclamptic women to create MoM.

Results

Of a total of 2,820 pregnant women included in the final analysis, 118 (4.18%) developed PE, of which 22 (0.78%) delivered before 34 weeks of gestation, 74 (2.62%) before 37 weeks, and 44 (1.56%) from 37 weeks gestation. Characteristics that significantly influenced PLGF were fetal crown rump length (CRL), maternal age, nulliparity, body mass index (BMI), chronic hypertension, Lupus, spontaneous pregnancy, polycystic ovary syndrome (PCOS), hypothyroidism, preeclampsia (PE) in a previous pregnancy, and mother with PE. MAP had significant influence from CRL, maternal age, PE in a previous pregnancy, induction of ovulation, a mother with PE, chronic hypertension, BMI, and hypothyroidism. UtA-PI was influenced by CRL, maternal age, a mother with PE, chronic hypertension, and gestational diabetes mellitus (GDM) in a previous pregnancy.

Conclusion

Population-specific multiples of the median (MoMs) for PlGF, MAP, and UtA-PI in the first trimester adequately discriminate among women developing preeclampsia later in pregnancy.
Ecotin: A versatile protease inhibitor of bacteria and eukaryotes
Authors: De Meyer Frédéric , Carlier Aurélien
Published: January 2023

Serine protease inhibitors are a large family of proteins involved in important pathways and processes, such as inflammatory responses and blood clotting. Most are characterized by a precise mode of action, thereby targeting a narrow range of protease substrates. However, the serine-protease inhibitor ecotin is able to inhibit a broad range of serine proteases that display a wide range of specificities. This specificity is driven by special structural features which allow unique flexibility upon binding to targets. Although frequently observed in many human/animal-associated bacteria, ecotin homologs may also be found in plant-associated taxa and environmental species. The purpose of this review is to provide an update on the biological importance, role in host–microbe interactions, and evolutionary relationship between ecotin orthologs isolated from Eukaryotic and Prokaryotic species across the Tree of Life.
Therapeutic potential of blocking GAPDH nitrosylation with CGP3466b in experimental autoimmune encephalomyelitis
Authors: Godfrey Wesley H. , Hwang Soonmyung , Cho Kaho , Shanmukha Shruthi , Gharibani Payam , Abramson Efrat , Kornberg Michael Davin
Published: January 2023

Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system (CNS). Although classically considered a demyelinating disease, neuroaxonal injury occurs in both the acute and chronic phases and represents a pathologic substrate of disability not targeted by current therapies. Nitric oxide (NO) generated by CNS macrophages and microglia contributes to neuroaxonal injury in all phases of MS, but candidate therapies that prevent NO-mediated injury have not been identified. Here, we demonstrate that the multifunctional protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is robustly nitrosylated in the CNS in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. GAPDH nitrosylation is blocked in vivo with daily administration of CGP3466b, a CNS-penetrant compound with an established safety profile in humans. Consistent with the known role of nitrosylated GAPDH (SNO-GAPDH) in neuronal cell death, blockade of SNO-GAPDH with CGP3466b attenuates neurologic disability and reduces axonal injury in EAE independent of effects on the immune system. Our findings suggest that SNO-GAPDH contributes to neuroaxonal injury during neuroinflammation and identify CGP3466b as a candidate neuroprotective therapy in MS.
Optic nerve sheath fenestration for visual impairment in cerebral venous diseases
Authors: Xue Xiao , Zhou Chen , Gao Yuan , Ji Xunming , Zhang Xuxiang
Published: January 2023

Objective

Visual impairment is the most common clinical feature of cerebral venous sinus occlusion or cerebral venous thrombosis-induced intracranial hypertension, which can result in optic atrophy, leading to irreversible vision loss, visual field defections, and finally, permanent blindness. Papilledema is a typical early pathophysiological alteration in visual impairment. Optic nerve sheath fenestration (ONSF) has become increasingly accepted as an option to prevent or halt progressive visual loss owing to its low risk and complications. The objective of this study is to review the latest research progress on ONSF for the treatment of visual impairment related to cerebral venous diseases.

Methods

Study were searched following PRISMA guidelines based on three electronic databases (Pubmed, Embase and Medline-Ovid). We used the following keywords and variations as keywords to identify studies: “optic nerve sheath fenestration, papilledema, cerebral venous diseases, cerebral venous stenosis, cerebral venous thrombosis, idiopathic intracranial hypertension”. The publication date of studies was restricted between 1,872.1.1 and 2,021.12.31. The application of ONSF in papilledema due to cerebral venous diseases is reviewed. Additionally, the common surgical approaches as well as advantages and disadvantages are also described graphically.

Results

With the improvement of specific details of the ONSF procedure and surgical instruments, complications of ONSF have reduced and its safety has been significantly improved, although the number of clinically investigated cases in the literature remains low.

Conclusion

We recommend that ONSF should be considered as an imperative alternative to reduce or delay the visual morbidity of cerebral venous diseases, although there is yet no consensus on the optimal surgical timing.
Aerobic exercise does not affect serum neurofilament light in patients with mild Alzheimer’s disease
Authors: Frederiksen Kristian Steen , Jensen Camilla Steen , Høgh Peter , Gergelyffy Robert , Waldemar Gunhild , Andersen Birgitte Bo , Gottrup Hanne , Vestergaard Karsten , Wermuth Lene , Søndergaard Helle Bach , Sellebjerg Finn , Hasselbalch Steen Gregers , Simonsen Anja Hviid
Published: January 2023

Introduction

Aerobic exercise has been shown to modify Alzheimer pathology in animal models, and in patients with multiple sclerosis to reduce neurofilament light (NfL), a biomarker of neurodegeneration.

Objective

To investigate whether a 16-week aerobic exercise program was able to reduce serum NfL in patients with mild Alzheimer’s disease (AD).

Methods

This is a secondary analysis of data from the multi-center Preserving Cognition, Quality of Life, Physical Health, and Functional Ability in Alzheimer’s disease: The Effect of Physical Exercise (ADEX) study. Participants were randomized to 16 weeks of moderate intensity aerobic exercise or usual care. Clinical assessment and measurement of serum NfL was done at baseline and after the intervention.

Results

A total of 136 participants were included in the analysis. Groups were comparable at baseline except for APOEε4 carriership which was higher in the usual care group (75.3 versus 60.2%; p = 0.04). There was no effect of the intervention on serum NfL [intervention: baseline NfL (pg/mL) 25.76, change from baseline 0.87; usual care: baseline 27.09, change from baseline −1.16, p = 0.09].

Conclusion

The findings do not support an effect of the exercise intervention on a single measure of neurodegeneration in AD. Further studies are needed using other types and durations of exercise and other measures of neurodegeneration.

Clinical trial registration

clinicaltrials.gov, identifier NCT01681602.
Adult neuroplasticity employs developmental mechanisms
Authors: Mowery Todd M. , Garraghty Preston E.
Published: January 2023

Although neural plasticity is now widely studied, there was a time when the idea of adult plasticity was antithetical to the mainstream. The essential stumbling block arose from the seminal experiments of Hubel and Wiesel who presented convincing evidence that there existed a critical period for plasticity during development after which the brain lost its ability to change in accordance to shifts in sensory input. Despite the zeitgeist that mature brain is relatively immutable to change, there were a number of examples of adult neural plasticity emerging in the scientific literature. Interestingly, some of the earliest of these studies involved visual plasticity in the adult cat. Even earlier, there were reports of what appeared to be functional reorganization in adult rat somatosensory thalamus after dorsal column lesions, a finding that was confirmed and extended with additional experimentation. To demonstrate that these findings reflected more than a response to central injury, and to gain greater control of the extent of the sensory loss, peripheral nerve injuries were used that eliminated ascending sensory information while leaving central pathways intact. Merzenich, Kaas, and colleagues used peripheral nerve transections to reveal unambiguous reorganization in primate somatosensory cortex. Moreover, these same researchers showed that this plasticity proceeded in no less than two stages, one immediate, and one more protracted. These findings were confirmed and extended to more expansive cortical deprivations, and further extended to the thalamus and brainstem. There then began a series of experiments to reveal the physiological, morphological and neurochemical mechanisms that permitted this plasticity. Ultimately, Mowery and colleagues conducted a series of experiments that carefully tracked the levels of expression of several subunits of glutamate (AMPA and NMDA) and GABA (GABAA and GABAB) receptor complexes in primate somatosensory cortex at several time points after peripheral nerve injury. These receptor subunit mapping experiments revealed that membrane expression levels came to reflect those seen in early phases of critical period development. This suggested that under conditions of prolonged sensory deprivation the adult cells were returning to critical period like plastic states, i.e., developmental recapitulation. Here we outline the heuristics that drive this phenomenon.
Association between the uric acid to high density lipoprotein cholesterol ratio and alanine transaminase in Chinese short stature children and adolescents: A cross-sectional study
Authors: Li Guangxin , Zhao Qianqian , Zhang Xinran , Ban Bo , Zhang Mei
Published: January 2023

Objective

Uric acid to high-density lipoprotein cholesterol ratio (UHR), the ratio of uric acid to high-density lipoprotein cholesterol, is a newly proposed marker of metabolic abnormalities. There are few previous studies directly investigating the relationship between UHR and alanine aminotransferase (ALT), especially in short stature populations, however, short stature children and adolescents are more likely to have metabolic disorders. This research aimed to investigate the relationship between the UHR and ALT in children and adolescents with short stature.

Methods

In this cross-sectional analysis, the clinical data of 1,510 children with height below −2 SD who were evaluated at the Department of Endocrinology, Affiliated Hospital of Jining Medical University from 1 March 2013 to 31 December 2021, were selected. Anthropometric and biochemical indicators were measured. The relationship between UHR and ALT was analysed.

Results

The univariate analysis results showed that UHR was positively associated with ALT (β = 0.43, P < 0.0001). Furthermore, after adjusting for possible confounding factors, a non-linear relationship was detected between UHR and ALT through smooth curve fitting, and the inflection point of UHR was 10.93% after multivariate piecewise linear regression analysis. ALT increased with UHR elevation when the UHR was greater than 10.93% (β = 0.69, 95% CI 0.39, 0.98; P < 0.0001). However, we did not observe a significant relationship when the UHR was less than 10.93% (P = 0.9229).

Conclusion

Our study demonstrated that in Chinese children and adolescents with short stature, UHR may be associated with the regulation of ALT levels, and this relationship merits further investigation.
Associations between dietary intake, physical activity, and obesity among public school teachers in Jeddah, Saudi Arabia
Authors: Almoraie Noha M. , Shatwan Israa M. , Althaiban Maha A. , Hanbazaza Mahitab A. , Wazzan Huda A. , Aljefree Najlaa M.
Published: January 2023

Objective

We aimed to assess the dietary intake of certain food groups in a representative sample of public-school teachers living in Jeddah city. We also, examined the association of dietary intake with physical activity and obesity among schoolteachers.

Methods

The study was a cross-sectional online survey, conducted among 640 (177 male, 463 female) schoolteachers aged between 20 and 62 years old and working in public primary, intermediate, and high schools in Jeddah. Measurements included gender, weight, height, body mass index (BMI), health problems, and lifestyle behaviours, including physical activity levels, smoking status, and dietary intake.

Results

Based on gender, number of non-smoking women (94%) was higher than number of non-smoking men (57.1%) (P < 0.001). However, men were more active than women (P = 0.03). Regarding BMI, there were more overweight men than women, while obese women numbered more than men (P = 0.003). There was no significant difference in dietary intake between men and women except that men consumed more soft drinks than women (P = 0.002). Lower physically active schoolteachers were less likely to consume salad (OR = 0.6, 95% CI 0.4–0.9; P = 0.02), vegetables (OR = 0.6, 95% CI 0.3–0.9; P = 0.01), beans and legumes (OR = 0.4, 95% CI 0.2–0.7; P = 0.005), wholegrain bread (OR = 0.6, 95% CI 0.4–0.9; P = 0.03), dairy products (OR = 0.6, 95% CI 0.4–0.9; P = 0.01), snacks (OR = 0.5, 95% CI 0.2–0.8; P = 0.01), and fish (OR = 0.4, 95% CI 0.2–0.9; P = 0.04) compared to those with high levels of physical activity. Only fruit intake was considered statistically significant (OR = 0.4, 95% CI 0.3–0.7; P = 0.003). The study found a relationship between the BMI of schoolteachers and food intake. Obese schoolteachers had lower consumption of fruits (OR = 0.3, 95% CI 0.2–0.7; P = 0.007) and white meat (OR = 0.5, 95%CI 0.3–0.9; P = 0.03) than schoolteachers in the normal weight group.

Conclusion

The high prevalence of physical activity, dietary intake and body weight among Saudi teachers is a major public health concern. The present study identified several lifestyle factors associated with body weight that may represent valid targets for the prevention and management of obesity among Saudi school teachers. Promoting active lifestyles and healthy diets would be primary targets for obesity prevention.
Microenvironment and the progress of immunotherapy in clinical practice of NSCLC brain metastasis
Authors: Xie Mengqing , Su Chunxia
Published: January 2023

One of the most frequent distant metastases of lung cancer occurs in the brain. The average natural survival duration for patients with lung cancer who have brain metastases is about 1 to 2 months. Knowledge about brain metastases is currently restricted since they are more difficult to acquire than other metastases. This review begins with an analysis of the immune microenvironment of brain metastases; focuses primarily on the functions of microglia, astrocytes, neurons, and tumor-infiltrating lymphocytes in the microenvironment of brain metastases; and offers an atlas of the immune microenvironment of brain metastases involving significant cells. In an effort to give researchers new research ideas, the study also briefly covers how immunotherapy for non-small cell lung cancer with brain metastases is currently faring.
HROP68: A rare case of medullary pancreatic cancer—characterization and chemosensitivity of the first patient-derived cell line
Authors: von den Driesch Jens , Flöttmann Jana , Prall Friedrich , Mullins Christina S. , Linnebacher Michael , Bürtin Florian
Published: January 2023

Introduction

Medullary pancreatic carcinoma (MPC) is a rare subtype of pancreatic ductal adenocarcinoma. MPCs represent less than 1% of all pancreatic cancers, and, with only 26 cases in the literature, knowledge regarding drug response and treatment outcome is very limited.

Material and methods

We present the case of a 64-year-old male patient with MPC who was treated by left pancreatic resection and adjuvant chemotherapy. Due to local recurrence, the patient underwent intended curative reoperation. From both surgical specimens, patient-derived xenografts (PDXs) and, from the recurrence, a patient-derived cell line (PDCL) were established. We subsequently performed an in-depth characterization of this cell line including phenotypic characterization, surface protein expression, growth, and migratory performance as well as mutational analysis using whole-exome sequencing (WES). Additionally, in vitro drug sensitivity toward the standard-of-care chemotherapeutic regimen and selected targeted therapies was evaluated.

Results

The pathological and molecular properties of this rare MPC case observed in the patient’s tumors are preserved in the corresponding PDX and the PDCL of HROP68Tu2. Despite displaying an “immunogenic phenotype” with marked T-cell infiltration and a high-level expression of HLA II and Programmed death-ligand 1 (PD-L1), molecular analysis revealed microsatellite stability but a multitude of mutations affecting KRAS, TP53, KAT6B, FOXG1, RUNX1, and GRIK2 among others. Furthermore, HROP68Tu2 cells were susceptible toward 5-FU, irinotecan, oxaliplatin, gemcitabine, paclitaxel, and erlotinib as single agents, but only a moderate synergistic response was seen to the drugs of the FOLFIRINOX regimen. Even worse, the drugs of the two combinations gemcitabine plus paclitaxel and gemcitabine plus erlotinib showed antagonistic effects. Moreover, lapatinib, PRIMA-Met1, and olaparib selected as targeted therapeutics according to the mutational profiles and protein expression inhibited HROP68Tu2 cells’ growth.

Conclusion

This study illustrates the establishment of the first preclinical MPC models as well as the first in-depth characterization of an MPC PDCL. Since the scientific and clinical knowledge of this rare pancreatic cancer type is very limited, the presented models contribute to a better understanding of MPC and might be a valuable tool for the development of future treatment options.
Progress on neoadjuvant immunotherapy in resectable non-small cell lung cancer and potential biomarkers
Authors: Wu Xinyu , Chau Yi Fung , Bai Hua , Zhuang Xiaofei , Wang Jie , Duan Jianchun
Published: January 2023

Immune checkpoint inhibitors (ICIs) are highly concerned in the treatment of non-small cell lung cancer (NSCLC), represented by inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), and inhibitors of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). The introduction of immunotherapy in the treatment of perioperative NSCLC has improved the prognosis to a great extent, as demonstrated by several phase II and III clinical trials. The target population for immunotherapy in early-stage NSCLC is still under discussion, and the biomarkers for neoadjuvant immunotherapy population selection are the next pending problem. The predictive efficacy of many potential makers is still being explored, including PD-L1 expression levels, tumor mutation burden, circulating tumor DNA, components of the tumor microenvironment, and several clinical factors. We summarize key findings on the utility of ICIs in clinical trials of preoperative NSCLC patients and conclude analyses of relevant biomarkers to provide a better understanding of potentially predictive biomarkers in neoadjuvant immunotherapy.
LAG-3+ tumor-infiltrating lymphocytes ameliorates overall survival in triple-negative breast cancer patients
Authors: Hu Guoming , Wang Shimin , Wang Songxiang , Ding Qiannan , Huang Liming
Published: January 2023

Purpose

Immune checkpoint molecule lymphocyte-activating gene-3 (LAG-3), which is expressed on active lymphocytes, has proven to be associated with immunosuppression and cancer progression in a variety of solid tumors. However, the role of LAG-3+ lymphocytes in human breast cancer (BC) is still not conclusive. We therefore performed a meta-analysis to clarify the role of these cells in prognosis prediction for BC.

Methods

We searched PubMed, Embase, and EBSCO to identify the studies evaluating the association of LAG-3+ lymphocyte infiltration and overall survival (OS) and/or disease-free survival (DFS) in BC patients, then combined extracted data with STATA 12.0.

Results

Eight published studies involving 5,859 BC patients were incorporated into this meta-analysis. We noted that a high number of LAG-3+ tumor-infiltrating lymphocytes were not appreciably associated with OS and DFS in BC patients. Strikingly, in stratified analyses based on the molecular type of BC, LAG-3+ lymphocyte infiltration was remarkably associated with better OS rather than DFS in triple-negative breast cancer (TNBC), whereas it significantly influenced neither OS nor DFS in Her2-positive BC. However, an increased density of these lymphocytes indicated a trend for better OS in Her2-positive BC. In addition, we found that LAG-3+ lymphocyte infiltration was also remarkably associated with prolonged OS in Her2-positive BC patients when they were measured by immunohistochemistry (IHC). In addition, an elevated number of these lymphocytes did not correlate with pathological complete response rate or clinicopathological features including lymph node metastasis.

Conclusion

The infiltration of LAG-3+ lymphocytes ameliorates OS in TNBC and Her2-positive BC, implicating that it is a valuable prognostic biomarker, and applications of anti-LAG-3 antagonists may possibly be not a promising therapeutic strategy for human BC especially for TNBC.
Predictors of residual disease after debulking surgery in advanced stage ovarian cancer
Authors: Abbas-Aghababazadeh Farnoosh , Sasamoto Naoko , Townsend Mary K. , Huang Tianyi , Terry Kathryn L. , Vitonis Allison F. , Elias Kevin M. , Poole Elizabeth M. , Hecht Jonathan L. , Tworoger Shelley S. , Fridley Brooke L.
Published: January 2023

Objective

Optimal debulking with no macroscopic residual disease strongly predicts ovarian cancer survival. The ability to predict likelihood of optimal debulking, which may be partially dependent on tumor biology, could inform clinical decision-making regarding use of neoadjuvant chemotherapy. Thus, we developed a prediction model including epidemiological factors and tumor markers of residual disease after primary debulking surgery.

Methods

Univariate analyses examined associations of 11 pre-diagnosis epidemiologic factors (n=593) and 24 tumor markers (n=204) with debulking status among incident, high-stage, epithelial ovarian cancer cases from the Nurses’ Health Studies and New England Case Control study. We used Bayesian model averaging (BMA) to develop prediction models of optimal debulking with 5x5-fold cross-validation and calculated the area under the curve (AUC).

Results

Current aspirin use was associated with lower odds of optimal debulking compared to never use (OR=0.52, 95%CI=0.31-0.86) and two tissue markers, ADRB2 (OR=2.21, 95%CI=1.23-4.41) and FAP (OR=1.91, 95%CI=1.24-3.05) were associated with increased odds of optimal debulking. The BMA selected aspirin, parity, and menopausal status as the epidemiologic/clinical predictors with the posterior effect probability ≥20%. While the prediction model with epidemiologic/clinical predictors had low performance (average AUC=0.49), the model adding tissue biomarkers showed improved, but weak, performance (average AUC=0.62).

Conclusions

Addition of ovarian tumor tissue markers to our multivariable prediction models based on epidemiologic/clinical data slightly improved the model performance, suggesting debulking status may be in part driven by tumor characteristics. Larger studies are warranted to identify those at high risk of poor surgical outcomes informing personalized treatment.
Lateral ventricle ectopic schwannoma: Case report and literature review
Authors: Li Yujian , Yang Xiang , Zhou Huiqing , Zheng Jun , Hui Xuhui , Li Hao , Liu Yanhui
Published: January 2023

Background

Cases of lateral ventricular ectopic schwannomas (LVES) are extremely rare, with only 23 cases reported thus far. This study aimed to obtain a better understanding of the disease.

Methods

We reported a rare case of LVES, in which the patient was admitted to our hospital, and reviewed the relevant literature on LVES to summarize and analyze the clinical manifestations, pathologies, imaging features and progress.

Results

Of the 23 patients, LVES was more common in men (74%, 17/23) than in women and was mostly located on the right side (78%, 18/23). The average age at clinical presentation was 28 years, with an age range between 8 and 68 years. Moreover, most cases were histologically benign, except in one case of malignancy. In all the benign cases, there were 2 cases of subtotal resection, but no recurrence was found during follow-up.

Conclusions

The origin of LVES could be the tumor transformation of autonomic nerve tissue in the perivascular choroid plexus. For lateral ventricle tumors,which are rare benign lesions with good prognosis after surgical resection, LVES should be considered in the differential diagnosis. Moreover, whether LVES could be considered for gamma knife treatment, similar to a small acoustic neuromas,requires further investigation.
When tissue is not the only issue: Poorly differentiated lung squamous-cell carcinoma with adrenal, costochondral, and cardiac metastases – case report
Authors: Clark Megan , Griborio-Guzman Andres G. , Burute Nishigandha P. , Lubbers Sonja , Anthes Margaret L. , Sadreddini Masoud , Aseyev Olexiy I.
Published: January 2023

Nonmelanoma skin cancer is the most common cancer in the world, and lung cancer is the leading cause of death from cancer. Histologically, squamous cell carcinoma (SCC) is the second most prevalent type of both skin and lung cancers. We report the case of a 38-year-old female with metastatic, poorly differentiated lung SCC detected on chest X-ray after she presented to the hospital with cough and dyspnea. She had had a 7.5 cm moderately differentiated well-circumscribed posterior scalp SCC completely excised eight years earlier. CT scan showed a large right lung mass, nodular filling defect in the left atrium (LA), and metastases to the adrenal glands and the first rib. Her pulmonary tumor extends to the LA via the right superior pulmonary vein, which is rarely reported in the literature. Ultrasound-guided biopsy of the rib mass showed poorly differentiated SCC. The patient received urgent radiotherapy, given superior vena cava and mainstem bronchus compression. Head CT showed no brain metastasis. A biopsy of the left adrenal initially reported an undifferentiated pleomorphic sarcoma; however, a second pathologist reported it as a poorly differentiated carcinoma of lung origin. At least three pathologists verified the specimen, and it had a PD-L1 test with a 1-49% score. An initial echocardiogram confirmed the LA mass. The patient received a Paclitaxel-Carboplatin-Pembrolizumab regimen as the first-line treatment for metastatic SCC. A repeat echocardiogram after cycle 1 showed a decrease in the size of the tumor in the LA. Almost five months after her initial visit, this young woman’s symptoms and performance status have improved post-palliative radiotherapy and chemo-immunotherapy. Follow-up CT showed smaller lung, nodal, adrenal, and costochondral masses, and evidence of necrosis. This case is clinically relevant because it represents a common problem presenting uncommonly. Moreover, it highlights that ultrasound-guided interventions and medical imaging are essential in directing metastatic cancer diagnosis, treatment, and follow-up, especially when pathology cannot confirm but only presume a specific diagnosis.
Phages against killer superbugs: An enticing strategy against antibiotics-resistant pathogens
Authors: Baral Bikash
Published: January 2023

The emerging resistivity of antibiotic resistance superbugs desire the need to resolve the global problem of antibiotic resistance. Among several other methods currently being adopted, one possible solution may be the development of supplemental therapies for antibiotics. The use of the normal and advanced bactericidal properties of bacteriophages (bacteriophage therapy) may be one of the viable infection control options. It is evident, however, that the safe and regulated application of phage treatment will need extensive knowledge of the characteristics and behaviour of certain phage–bacterium systems. This mini review offers an overview of the potential for phage therapy as well as the constraints and obstacles it faces in becoming a commonly accepted infection management strategy.
Neuronal activity of the medial prefrontal cortex, nucleus accumbens, and basolateral amygdala in conditioned taste aversion and conditioned place preference induced by different doses of morphine administrations in rats
Authors: Ou Chen Yin , Yu Ying Hao , Wu Chi-Wen , Kozłowska Anna , Shyu Bai-Chung , Huang Andrew Chih Wei
Published: January 2023

To re-examine the paradoxical effect hypothesis of abused drugs, the present study concerned whether different doses of morphine disparately affect neuronal activity and associations among the subareas of the medial prefrontal cortex (mPFC: cingulate cortex 1-Cg1, prelimbic cortex-PrL, infralimbic cortex-IL), the subregions of the nucleus accumbens (NAc; both core and shell), and the basolateral amygdala (BLA) following conditioned taste aversion (CTA) and conditioned place preference (CPP). All rats were given a 0.1% saccharin solution for 15-min, and they were intraperitoneally injected with saline or 20, 30, or 40 mg/kg morphine to form the aversive CTA learning. Later, half of the rats were tested for CPP (including the CTA and then CPP tests) for 30-min. Finally, the immunohistochemical staining with c-Fos was conducted after the behavioral test. After the CTA test, c-Fos (%) in the Cg1 and PrL (but not the IL) was more in 20–40 mg/kg of the morphine groups; c-Fos (%) in the NAc core, NAc shell, and BLA was more in the 30–40 mg/kg morphine group. After the CPP test, the Cg1, PrL, IL, and BLA showed more c-Fos (%) in 20 mg/kg morphine; the NAc core showed fewer in c-Fos (%) in the 30–40 mg/kg morphine groups. The mPFC subregions (e.g., Cg1, PrL, and IL), NAc subareas (e.g., NAc core and NAc shell), and BLA were involved in the different doses of morphine injections. The correlation analysis showed that a positive correlation was observed between PrL and IL with NAc core with low doses of morphine and with NAc shell with increasing doses of morphine after the CTA test. After the CPP, an association between PrL and NAc core and NAc shell at low doses and between IL and BLA and NAc shell with increasing doses of morphine. Therefore, different neural substrates and the neural connectivity are observed following different doses of morphine and after the CTA and CPP tests. The present data extend the paradoxical effect hypothesis of abused drugs.