bluuebunny/crossref_metadata_2025 huggingface dataset:
The clinical and therapeutic profiles of prolactinomas associated with germline pathogenic variants in the aryl hydrocarbon receptor interacting protein (AIP) gene
Authors: Vroonen Laurent , Beckers Albert , Camby Severine , Cuny Thomas , Beckers Pablo , Jaffrain-Rea Marie-Lise , Cogne Muriel , Naves Luciana , Ferriere Amandine , Romanet Pauline , Elenkova Atanaska , Karhu Auli , Brue Thierry , Barlier Anne , Pétrossians Patrick , Daly Adrian F.
Published: August 2023

Introduction

Prolactinomas are the most frequent type of pituitary adenoma encountered in clinical practice. Dopamine agonists (DA) like cabergoline typically provide sign/ symptom control, normalize prolactin levels and decrease tumor size in most patients. DA-resistant prolactinomas are infrequent and can occur in association with some genetic causes like MEN1 and pathogenic germline variants in the AIP gene (AIPvar).

Methods

We compared the clinical, radiological, and therapeutic characteristics of AIPvar-related prolactinomas (n=13) with unselected hospital-treated prolactinomas (“unselected”, n=41) and genetically-negative, DA-resistant prolactinomas (DA-resistant, n=39).

Results

AIPvar-related prolactinomas occurred at a significantly younger age than the unselected or DA-resistant prolactinomas (p<0.01). Males were more common in the AIPvar (75.0%) and DA- resistant (49.7%) versus unselected prolactinomas (9.8%; p<0.001). AIPvar prolactinomas exhibited significantly more frequent invasion than the other groups (p<0.001) and exhibited a trend to larger tumor diameter. The DA-resistant group had significantly higher prolactin levels at diagnosis than the AIPvar group (p<0.001). Maximum DA doses were significantly higher in the AIPvar and DA-resistant groups versus unselected. DA-induced macroadenoma shrinkage (>50%) occurred in 58.3% in the AIPvar group versus 4.2% in the DA-resistant group (p<0.01). Surgery was more frequent in the AIPvar and DA- resistant groups (43.8% and 61.5%, respectively) versus unselected (19.5%: p<0.01). Radiotherapy was used only in AIPvar (18.8%) and DA-resistant (25.6%) groups.

Discussion

AIPvar confer an aggressive phenotype in prolactinomas, with invasive tumors occurring at a younger age. These characteristics can help differentiate rare AIPvar related prolactinomas from DA-resistant, genetically-negative tumors.
Identification and immunogenic potential of glycosylphosphatidylinositol-anchored proteins in Paracoccidioides brasiliensis
Authors: Gonçales Relber Aguiar , Portis Igor Godinho , dos Reis Thaila Fernanda , Basso Júnior Luiz Roberto , Martinez Roberto , Zhu Heng , Pereira Maristela , Soares Célia Maria de Almeida , Coelho Paulo Sergio Rodrigues
Published: August 2023

In fungal pathogens the cell wall plays an important role in host-pathogen interactions because its molecular components (e.g., polysaccharides and proteins) may trigger immune responses during infection. GPI-anchored proteins represent the main protein class in the fungal cell wall where they can perform several functions, such as cell wall remodeling and adhesion to host tissues. Genomic analysis has identified the complement of GPI-anchored proteins in many fungal pathogens, but the function has remained unknown for most of them. Here, we conducted an RNA expression analysis of GPI-anchored proteins of Paracoccidioides brasiliensis which causes paracoccidioidomycosis (PCM), an important human systemic mycosis endemic in Latin America. The expression of the GPI-anchored proteins was analyzed by quantitative PCR in both the mycelium and yeast forms. qPCR analysis revealed that the transcript levels of 22 of them were increased in hyphae and 10 in yeasts, respectively, while 14 did not show any significant difference in either form. Furthermore, we cloned 46 open reading frames and purified their corresponding GPI-anchored proteins in the budding yeast. Immunoblot and ELISA analysis of four purified GPI-anchored proteins revealed immune reactivity of these proteins against sera obtained from PCM patients. The information obtained in this study provides valuable information about the expression of many GPI-anchored proteins of unknown function. In addition, based on our immune analysis, some GPI-anchored proteins are expressed during infection and therefore, they might serve as good candidates for the development of new diagnostic methods.
Cellular immunity to SARS-CoV-2 following intrafamilial exposure in seronegative family members
Authors: Jay Cecilia , Adland Emily , Csala Anna , Dold Christina , Edmans Matthew , Hackstein Carl-Philipp , Jamsen Anni , Lim Nicholas , Longet Stephanie , Ogbe Ane , Sampson Oliver , Skelly Donal , Spiller Owen B. , Stafford Lizzie , Thompson Craig P. , Turtle Lance , Barnes Ellie , Dunachie Susanna , Carroll Miles , Klenerman Paul , Conlon Chris , Goulder Philip , Jones Lucy C.
Published: August 2023

Introduction

Family studies of antiviral immunity provide an opportunity to assess virus-specific immunity in infected and highly exposed individuals, as well as to examine the dynamics of viral infection within families. Transmission of SARS-CoV-2 between family members represented a major route for viral spread during the early stages of the pandemic, due to the nature of SARS-CoV-2 transmission through close contacts.

Methods

Here, humoral and cellular immunity is explored in 264 SARS-CoV-2 infected, exposed or unexposed individuals from 81 families in the United Kingdom sampled in the winter of 2020 before widespread vaccination and infection.

Results

We describe robust cellular and humoral immunity into COVID-19 convalescence, albeit with marked heterogeneity between families and between individuals. T-cell response magnitude is associated with male sex and older age by multiple linear regression. SARS-CoV-2-specific T-cell responses in seronegative individuals are widespread, particularly in adults and in individuals exposed to SARS-CoV-2 through an infected family member. The magnitude of this response is associated with the number of seropositive family members, with a greater number of seropositive individuals within a family leading to stronger T-cell immunity in seronegative individuals.

Discussion

These results support a model whereby exposure to SARS-CoV-2 promotes T-cell immunity in the absence of an antibody response. The source of these seronegative T-cell responses to SARS-CoV-2 has been suggested as cross-reactive immunity to endemic coronaviruses that is expanded upon SARS-CoV-2 exposure. However, in this study, no association between HCoV-specific immunity and seronegative T-cell immunity to SARS-CoV-2 is identified, suggesting that de novo T-cell immunity may be generated in seronegative SARS-CoV-2 exposed individuals.
M-STCP: an online ship trajectory cleaning and prediction algorithm using matrix neural networks
Authors: Guo Shuai , Sun Meng , Xue Huanqun , Mao Xiaodong , Wang Shuang , Liu Chao
Published: August 2023

Accurate prediction of ship trajectories is crucial to guarantee the safety of maritime navigation. In this paper, a matrix neural network-based online ship track cleaning and prediction algorithm called M-STCP is suggested to forecast ship tracks. Firstly, the GPS-provided historical ship trajectory data is cleaned, and the data cleaning process is finished using the anomaly point algorithm. Secondly, the trajectory is input into the matrix neural network for training and prediction, and the algorithm is improved by using Kalman filtering, which reduces the influence of noise on the prediction results and improves the prediction accuracy. In the end, the effectiveness of the method is verified using real GPS trajectory data, and compared with the GRU model and long-short-term memory networks. The M-STCP method can improve the prediction accuracy of ship trajectory to 89.44%, which is 5.17% higher than LSTM and 1.82% higher than GRU, effectively improving the prediction accuracy and time efficiency.
First insights into the population characteristics and seasonal occurrence of the great hammerhead shark, Sphyrna mokarran (Rüppell, 1837) in the Western Tuamotu archipelago, French Polynesia
Authors: Boube Tatiana , Azam Claire-Sophie , Guilbert Antonin , Huveneers Charlie , Papastamatiou Yannis P. , Mourier Johann , Trujillo José E. , Femmami Nastazia , Kunovsky Andréa , Bersani Florent , Laurent Enzo , Bousseyroux Alice , Thellier Thibaut , Follin Yann , Pavy Thomas , Jeandel Virginie , Mataarere Alexander , Burlot Manuella , Bouyeure Jordan , Rigoreau Béatrice , Rigoreau Laurent , Lenormand Audrey , Chalabi Farid , Hayek Marc , Jeandel Jean-Marie , Stenger Pierre-Louis
Published: August 2023

The occurrence and seasonality of the Critically Endangered great hammerhead shark, Sphyrna mokarran, is data deficient in the Central Pacific region. Using photo-identification and laser-photogrammetry, we describe the seasonal population of great hammerhead sharks in the Tiputa pass (Rangiroa atoll) and Tuheiava pass (Tikehau atoll) in the Tuamotu archipelago of French Polynesia. During the austral summer of 2020 and 2021, we recorded a female-biased aggregation of at least 55 individuals (54 females; 1 unknown sex), representing an unprecedented number of S. mokarran in one study. All measured sharks were likely mature with pre-caudal lengths ranging from 147 cm to 297 cm (n = 35). Videos from citizen scientists recorded over a 15-year period enable us to identify 30 additional individuals between 2006 and 2019, with strong evidence of sexual segregation during the year. Our findings revealed seasonal residency (n = 32) of up to 6 days/month and for up to 5 months at the study site during the austral summer. We also demonstrated site fidelity with 32 individuals returning to the same atoll for up to 12 years between the first and last sighting, and with limited evidence of connectivity between the two sites. Our analysis also provides preliminary insight into the environmental factors driving S. mokarran aggregation in the Tiputa pass, suggesting a marked influence of the lunar cycle and of ocellated eagle rays (Aetobatus ocellatus) abundance. This study, conducted in situ with non-invasive methods offers a unique opportunity to study a great hammerhead shark population in a near-pristine ecosystem and provides important life-history elements for the Central Pacific region.
Non-alcoholic fatty liver disease fibrosis score is a useful index for predicting all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Whang Jeong Yeop , Park Pil Gyu , Park Yong-Beom , Huh Ji Hye , Lee Sang-Won
Published: August 2023

Background

This study investigated whether the non-alcoholic fatty liver disease fibrosis score (NFS) could predict all-cause mortality during follow-up among patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods

The medical records of 256 AAV patients were retrospectively reviewed. AAV patients with clinically critical chronic liver diseases were excluded. NFS was calculated using the following equation: NFS = −1.675 + 0.037 - age + 0.094 – body mass index +1.13 × impaired fasting glucose/diabetes mellitus +0.99 × aspartate aminotransferase/alanine aminotransferase ratio - 0.013 × platelet count - 0.66 × serum albumin.

Results

The median age was 59.0 years, and 35.2% of the patients were male. The median Birmingham Vasculitis Activity Score (BVAS), five-factor score (FFS), and NFS were 12.0, 1.0, and − 4.7, respectively. Of the 256 patients, 33 (12.9%) died. Using the receiver operating characteristic curve, the optimal cut-off of NFS for all-cause mortality was obtained as-3.97. AAV patients with NFS at diagnosis ≥ − 3.97 exhibited a lower cumulative patients’ survival rate than those with NFS at diagnosis <−3.97. The multivariable Cox analysis revealed that NFS at diagnosis ≥ − 3.97 (HR 2.232, 95% CI 1.011, 4.925) was independently associated with all-cause mortality in AAV patients.

Conclusion

This study was the first to demonstrate that NFS at AAV diagnosis was clinically useful in predicting all-cause mortality during follow-up, regardless of both the degree of liver fibrosis and abnormal or normal liver function results.
Atelectasis in obese patients undergoing laparoscopic bariatric surgery are not increased upon discharge from Post Anesthesia Care Unit
Authors: Braun Matthias , Ruscher Lea , Fuchs Alexander , Kämpfer Martina , Huber Markus , Luedi Markus M. , Riva Thomas , Vogt Andreas , Riedel Thomas
Published: August 2023

Background

Obese patients frequently develop pulmonary atelectasis upon general anesthesia. The risk is increased during laparoscopic surgery. This prospective, observational single-center study evaluated atelectasis dynamics using Electric Impedance Tomography (EIT) in patients undergoing laparoscopic bariatric surgery.

Methods

We included adult patients with ASA physical status I–IV and a BMI of ≥40. Exclusion criteria were known severe pulmonary hypertension, home oxygen therapy, heart failure, and recent pulmonary infections. The primary outcome was the proportion of poorly ventilated lung regions (low tidal variation areas) and the global inhomogeneity (GI) index assessed by EIT before discharge from the Post Anesthesia Care Unit compared to these same measures prior to initiation of anesthesia.

Results

The median (IQR) proportion of low tidal variation areas at the different analysis points were T1 10.8% [3.6–15.1%] and T5 10.3% [2.6–18.9%], and the mean difference was −0.7% (95% CI: −5.8% −4.5%), i.e., lower than the predefined non-inferiority margin of 5% (p = 0.022). There were no changes at the four additional time points compared to T1 or postoperative pulmonary complications during the 14 days following the procedure.

Conclusion

We found that obese patients undergoing laparoscopic bariatric surgery do not leave the Post Anesthesia Care Unit with increased low tidal variation areas compared to the preoperative period.
Contribution of potassium solubilizing bacteria in improved potassium assimilation and cytosolic K+/Na+ ratio in rice (Oryza sativa L.) under saline-sodic conditions
Authors: Nawaz Aniqa , Qamar Zia Ul , Marghoob Muhammad Usama , Imtiaz Muhammad , Imran Asma , Mubeen Fathia
Published: August 2023

Sodium-induced potassium (K+) deficiency is more prevalent in salt-affected soils. Plants experience K+ starvation thus cytosolic K+/Na+ ratio is lowered, which is a prerequisite for their survival. K+ enrichment in crops can be acquired via K-solubilizing bacteria as a sustainable green agriculture approach. This study was conducted to explore potent K-solubilizing bacteria from the rhizosphere of wheat, rice, and native flora grown in salt-affected soils in two distinct regions of Pakistan. The aim of this work was to evaluate the contribution of microbial consortiums to the improvement of K+ assimilation and cytosolic K+/Na+ ratios in rice crops under saline-sodic conditions. Among 250 bacterial isolates, 9 were selected based on their salt (11% NaCl) and alkali (9) tolerance and K-solubilization indices (1.57–5.67). These bacterial strains were characterized for their plant growth-promoting traits and identified based on 16S rRNA gene sequencing. A consortium of five strains, namely, Enterobacter hormaechei, Citrobacter braakii, Pseudomonas putida, Erwinia iniecta, and Pantoea agglomerans, was used as a bio-inoculant to evaluate its role in K+ assimilation, cytosolic K+/Na+ ratio, and subsequent yield enhancement in rice grown under saline-sodic conditions. The impact of applied consortium on rice was assessed under variable salt levels (Control, 40, 80, and 120 mM) in a pot experiment and under natural saline-sodic conditions in the field. Plant agronomical parameters were significantly higher in the bacterial consortium-treated plants, with a concomitant increase in K+-uptake in root and shoot (0.56 and 0.35 mg g−1 dry wt.) of the salt-tolerant rice variety Shaheen. The root K+/Na+ ratio was significantly improved (200% in 40 mM and 126% in 80 mM NaCl) and in the shoot (99% in 40 mM and 131% in 80 mM) too. A similar significant increase was also observed in the salt-susceptible variety Kainat. Moreover, grain yield (30.39 g/1,000 grains wt.) and biomass (8.75 g) of the rice variety Shaheen, grown in field conditions, were also improved. It can be concluded that K-solubilizing bacteria can be used as bio-inoculants, contributing to growth and yield increment via enhanced K-assimilation and cytosolic K+/Na+ ratio in rice crops under salt stress.
The mutational profile in a South African cohort with inherited neuropathies and spastic paraplegia
Authors: Mahungu Amokelani C. , Steyn Elizabeth , Floudiotis Niki , Wilson Lindsay A. , Vandrovcova Jana , Reilly Mary M. , Record Christopher J. , Benatar Michael , Wu Gang , Raga Sharika , Wilmshurst Jo M. , Naidu Kireshnee , Hanna Michael , Nel Melissa , Heckmann Jeannine M.
Published: August 2023

Introduction

Limited diagnostics are available for inherited neuromuscular diseases (NMD) in South Africa and (excluding muscle disease) are mainly aimed at the most frequent genes underlying genetic neuropathy (GN) and spastic ataxias in Europeans. In this study, we used next-generation sequencing to screen 61 probands with GN, hereditary spastic paraplegia (HSP), and spastic ataxias for a genetic diagnosis.

Methods

After identifying four GN probands with PMP22 duplication and one spastic ataxia proband with SCA1, the remaining probands underwent whole exome (n = 26) or genome sequencing (n = 30). The curation of coding/splice region variants using gene panels was guided by allele frequencies from internal African-ancestry control genomes (n = 537) and the Clinical Genome Resource's Sequence Variant Interpretation guidelines.

Results

Of 32 GN probands, 50% had African-genetic ancestry, and 44% were solved: PMP22 (n = 4); MFN2 (n = 3); one each of MORC2, ATP1A1, ADPRHL2, GJB1, GAN, MPZ, and ATM. Of 29 HSP probands (six with predominant ataxia), 66% had African-genetic ancestry, and 48% were solved: SPG11 (n = 3); KIF1A (n = 2); and one each of SPAST, ATL1, SPG7, PCYT2, PSEN1, ATXN1, ALDH18A1, CYP7B1, and RFT1. Structural variants in SPAST, SPG11, SPG7, MFN2, MPZ, KIF5A, and GJB1 were excluded by computational prediction and manual visualisation.

Discussion

In this preliminary cohort screening panel of disease genes using WES/WGS data, we solved ~50% of cases, which is similar to diagnostic yields reported for global cohorts. However, the mutational profile among South Africans with GN and HSP differs substantially from that in the Global North.
Brain nuclei and neural circuits in neuropathic pain and brain modulation mechanisms of acupuncture: a review on animal-based experimental research
Authors: Su Na , Cai Pingping , Dou Zhiqiang , Yin Xiaoxue , Xu Hongmin , He Jing , Li Zhaofeng , Li Changzhong
Published: August 2023

Neuropathic pain (NP) is known to be associated with abnormal changes in specific brain regions, but the complex neural network behind it is vast and complex and lacks a systematic summary. With the help of various animal models of NP, a literature search on NP brain regions and circuits revealed that the related brain nuclei included the periaqueductal gray (PAG), lateral habenula (LHb), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC); the related brain circuits included the PAG-LHb and mPFC-ACC. Moreover, acupuncture and injurious information can affect different brain regions and influence brain functions via multiple aspects to play an analgesic role and improve synaptic plasticity by regulating the morphology and structure of brain synapses and the expression of synapse-related proteins; maintain the balance of excitatory and inhibitory neurons by regulating the secretion of glutamate, γ-aminobutyric acid, 5-hydroxytryptamine, and other neurotransmitters and receptors in the brain tissues; inhibit the overactivation of glial cells and reduce the release of pro-inflammatory mediators such as interleukins to reduce neuroinflammation in brain regions; maintain homeostasis of glucose metabolism and regulate the metabolic connections in the brain; and play a role in analgesia through the mediation of signaling pathways and signal transduction molecules. These factors help to deepen the understanding of NP brain circuits and the brain mechanisms of acupuncture analgesia.
Bitter taste receptors along the gastrointestinal tract: comparison between humans and rodents
Authors: Descamps-Solà Maria , Vilalta Adrià , Jalsevac Florijan , Blay M. Teresa , Rodríguez-Gallego Esther , Pinent Montserrat , Beltrán-Debón Raúl , Terra Ximena , Ardévol Anna
Published: August 2023

For decades bitter taste receptors (TAS2R) were thought to be located only in the mouth and to serve as sensors for nutrients and harmful substances. However, in recent years Tas2r have also been reported in extraoral tissues such as the skin, the lungs, and the intestine, where their function is still uncertain. To better understand the physiological role of these receptors, in this paper we focused on the intestine, an organ in which their activation may be similar to the receptors found in the mouth. We compare the relative presence of these receptors along the gastrointestinal tract in three main species of biomedical research (mice, rats and humans) using sequence homology. Current data from studies of rodents are scarce and while more data are available in humans, they are still deficient. Our results indicate, unexpectedly, that the reported expression profiles do not always coincide between species even if the receptors are orthologs. This may be due not only to evolutionary divergence of the species but also to their adaptation to different dietary patterns. Further studies are needed in order to develop an integrated vision of these receptors and their physiological functionality along the gastrointestinal tract.
Association between fish intake and prevalence of frailty in community-dwelling older adults after 4-year follow-up: the Korean frailty and aging cohort study
Authors: Ahn Jeonghwan , Kim Miji , Won Chang Won , Park Yongsoon
Published: August 2023

Cross-sectional epidemiological studies suggested the intake of fish and seafood was negatively associated with the prevalence of frailty. This study aimed to investigate the hypothesis that the prevalence of frailty is negatively associated with the consumption of total seafood and fish at baseline and 4-year follow-up. Using a multicenter longitudinal study of community-dwelling Korean adults aged 70–84 years old, 953 participants at baseline and 623 participants at 4-year follow-up were included after excluding participants without data on frailty or dietary intake in the Korean Frailty and Aging Cohort Study. Frailty was defined using the Cardiovascular Health Study index, and participants with scores ≥3 were considered frail. The trained dietitians obtained two non-consecutive 24-h dietary recalls during spring and fall at baseline. The prevalence of frailty was 13.5%. The intake of fish (OR 0.47; 95% CI 0.24–0.91; p for trend = 0.028) and total seafood (OR 0.34; 95% CI 0.18–0.68; p for trend = 0.002) at baseline was associated with frailty at 4-year follow-up after adjusting for the confounding factors. The intake of fish and total seafood at the baseline was negatively associated with the prevalence of exhaustion, low handgrip strength, and slow gait speed at 4-year follow-up. However, shellfish intake was not associated with frailty. In addition, the intake of fish, shellfish, and total seafood did not differ among the frailty transition groups in terms of deterioration, persistence, and reversal. The total consumption of seafood, particularly fish, could be beneficial for preventing frailty in Korean community-dwelling older adults. In particular, the consumption of fish (total seafood) at baseline could be beneficial for preventing exhaustion, low handgrip strength, and slow gait speed at 4-year follow-up.
Comparison between regular additional endobiliary radiofrequency ablation and photodynamic therapy in patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy
Authors: Möhring Christian , Khan Oliver , Zhou Taotao , Sadeghlar Farsaneh , Mahn Robert , Kaczmarek Dominik J. , Dold Leona , Toma Marieta , Marinova Milka , Glowka Tim R. , Matthaei Hanno , Manekeller Steffen , Kalff Jörg C. , Strassburg Christian P. , Weismüller Tobias J. , Gonzalez-Carmona Maria A.
Published: August 2023

Background and aims

Extrahepatic cholangiocarcinoma (eCCA) remains a malignancy with a dismal prognosis. The first-line standard of care includes systemic chemotherapy (SC) and biliary drainage through stenting. Endobiliary ablative techniques, such as photodynamic therapy (ePDT) and radio-frequency ablation (eRFA), have demonstrated feasibility and favorable survival data. This study aimed to compare the oncologic outcome in patients treated with SC and concomitant eRFA or ePDT.

Method

All patients with eCCA were evaluated for study inclusion. Sixty-three patients receiving a combination of SC and at least one endobiliary treatment were retrospectively compared.

Results

Patients were stratified into three groups: SC + ePDT (n = 22), SC + eRFA (n = 28), and SC + ePDT + eRFA (n = 13). The median overall survival (OS) of the whole cohort was 14.2 months with no statistically significant difference between the three therapy groups but a trend to better survival for the group receiving ePDT as well as eRFA, during SC (ePDT + SC, 12.7 months; eRFA + SC, 13.8 months; ePDT + eRFA + SC, 20.2 months; p = 0.112). The multivariate Cox regression and subgroup analysis highlighted the beneficial effect of eRFA on OS. Overall, combined therapy was well tolerated. Only cholangitis occurred more often in the SC + eRFA group.

Conclusion

Additional endobiliary ablative therapies in combination with SC were feasible. Both modalities, eRFA and ePDT, showed a similar benefit in terms of survival. Interestingly, patients receiving both regimes showed the best OS indicating a possible synergism between both ablative therapeutic techniques.
Evaluation of the anterior and overall tooth ratios in the Saudi population versus Bolton's standards
Authors: Awawdeh Mohammed , Alsaadi Waad , Alraddadi Faris Awadh B. , Alshunaiber Renad , Alessa Jood , Alsaeed Suliman
Published: August 2023

Understanding tooth-size discrepancy is essential in the process of diagnosis of maxillary and mandibular relationship. Due to the high incidence of tooth-size disproportion, Practitioners should consider the high incidence of tooth-size disproportion when planning treatment for their patients, as in many cases, this can be a hindrance to obtaining an ideal result. This study aimed to determine the anterior and overall tooth ratios in the Saudi population and compare them with Bolton's standards. A total of 356 patients were recruited. For the anterior ratio, around 25% of the patients had a ratio equal to Bolton's standards (77.2%). Most subjects (53.7%) had a ratio above 77.2%, and the remaining (20%) had a ratio below 77.2%. The mean amount of anterior mandibular excess was 2.17 ± 2.12 mm, and the mean amount of anterior maxillary excess was 2.16 ± 2.08 mm. For the overall ratio, less than half of the participants (43%) had a ratio equal to Bolton's standards (91.3%). Almost 34% had a ratio above 91.3%, while 23% of the participants had a ratio below 91.3%. The mean amount of overall mandibular excess was 2.54 ± 2.37 mm, and the mean amount of overall maxillary excess was 3.31 ± 3.33 mm. The majority of the study sample had an overall and anterior Bolton ratio that is different from the norms of Bolton's standards, with a tendency for increased overall and anterior ratios. Having specific standards for the Saudi population is important for better clinical assessment and treatment outcomes.
Feasibility of combination of Gun-Chil-Jung and cytokine-induced killer cells-based immunotherapy for terminal hepatocellular carcinoma patient: a case report
Authors: Park Chan-Ran , Bae Hye-Ri , Lee Ga-Young , Son Chang-Gue , Cho Jung-Hyo , Cho Chong-Kwan , Lee Nam-Hun
Published: August 2023

Introduction: Terminal-stage hepatocellular carcinoma (HCC) is inoperable and currently has no form of adjuvant therapy. This study examined the anticancer herbal extract Gun-Chil-Jung (GCJ) combined with cytokine-induced killer (CIK)-cell-based immunotherapy as a palliative therapy for terminal HCC. We report the case of an HCC patient with extended overall survival and improved symptoms and tumor marker levels following combination therapy with GCJ and CIK cell-based immunotherapy.

Baseline Characteristics: From March to July 2020, a 57-year-old man who had been diagnosed with HCC underwent combination treatment with GCJ and CIK cell-based immunotherapy. By August 2021, he was prescribed GCJ. After treatment, the patient’s condition was evaluated with respect to overall survival, tumor markers, symptoms, abdominal computed tomography findings, chest x-ray results, and Eastern Cooperative Oncology Group (ECOG) grade.

Results: The patient’s overall survival, tumor marker levels, ECOG grade, and symptoms, including ascites, lower limb edema, jaundice, pleural effusion, and fatigue, were largely alleviated.

Conclusion: We expect that this combination therapy may be an option for palliative therapy of terminal HCC.
Epac induces ryanodine receptor-dependent intracellular and inter-organellar calcium mobilization in mpkCCD cells
Authors: Yip Kay-Pong , Ribeiro-Silva Luisa , Cha Byeong , Rieg Timo , Sham James S. K.
Published: August 2023

Arginine vasopressin (AVP) induces an increase in intracellular Ca2+ concentration ([Ca2+]i) with an oscillatory pattern in isolated perfused kidney inner medullary collecting duct (IMCD). The AVP-induced Ca2+ mobilization in inner medullary collecting ducts is essential for apical exocytosis and is mediated by the exchange protein directly activated by cyclic adenosine monophosphate (Epac). Murine principal kidney cortical collecting duct cells (mpkCCD) is the cell model used for transcriptomic and phosphoproteomic studies of AVP signaling in kidney collecting duct. The present study examined the characteristics of Ca2+ mobilization in mpkCCD cells, and utilized mpkCCD as a model to investigate the Epac-induced intracellular and intra-organellar Ca2+ mobilization. Ca2+ mobilization in cytosol, endoplasmic reticulum lumen, and mitochondrial matrix were monitored with a Ca2+ sensitive fluorescent probe and site-specific Ca2+ sensitive biosensors. Fluorescence images of mpkCCD cells and isolated perfused inner medullary duct were collected with confocal microscopy. Cell permeant ligands of ryanodine receptors (RyRs) and inositol 1,4,5 trisphosphate receptors (IP3Rs) both triggered increase of [Ca2+]i and Ca2+ oscillations in mpkCCD cells as reported previously in IMCD. The cell permeant Epac-specific cAMP analog Me-cAMP/AM also caused a robust Ca2+ mobilization and oscillations in mpkCCD cells. Using biosensors to monitor endoplasmic reticulum (ER) luminal Ca2+ and mitochondrial matrix Ca2+, Me-cAMP/AM not only triggered Ca2+ release from ER into cytoplasm, but also shuttled Ca2+ from ER into mitochondria. The Epac-agonist induced synchronized Ca2+ spikes in cytosol and mitochondrial matrix, with concomitant declines in ER luminal Ca2+. Me-cAMP/AM also effectively triggered store-operated Ca2+ entry (SOCE), suggesting that Epac-agonist is capable of depleting ER Ca2+ stores. These Epac-induced intracellular and inter-organelle Ca2+ signals were mimicked by the RyR agonist 4-CMC, but they were distinctly different from IP3R activation. The present study hence demonstrated that mpkCCD cells retain all reported features of Ca2+ mobilization observed in isolated perfused IMCD. It further revealed information on the dynamics of Epac-induced RyR-dependent Ca2+ signaling and ER-mitochondrial Ca2+ transfer. ER-mitochondrial Ca2+ coupling may play a key role in the regulation of ATP and reactive oxygen species (ROS) production in the mitochondria along the nephron. Our data suggest that mpkCCD cells can serve as a renal cell model to address novel questions of how mitochondrial Ca2+ regulates cytosolic Ca2+ signals, inter-organellar Ca2+ signaling, and renal tubular functions.
Large effect of phosphate-solubilizing bacteria on the growth and gene expression of Salix spp. at low phosphorus levels
Authors: Koczorski Piotr , Furtado Bliss Ursula , Baum Christel , Weih Martin , Ingvarsson Pär , Hulisz Piotr , Hrynkiewicz Katarzyna
Published: August 2023

Phosphorus is one of the most important nutrients required for plant growth and development. However, owing to its low availability in the soil, phosphorus is also one of the most difficult elements for plants to acquire. Phosphorus released into the soil from bedrock quickly becomes unavailable to plants, forming poorly soluble complexes. Phosphate-solubilizing bacteria (PSB) can solubilize unavailable phosphorus-containing compounds into forms in which phosphorus is readily available, thus promoting plant growth. In this study, two willow species, Salix dasyclados cv. Loden and Salix schwerinii × Salix viminalis cv. Tora, were inoculated with two selected bacterial strains, Pantoea agglomerans and Paenibacillus spp., to evaluate the plant growth parameters and changes in gene expression in the presence of different concentrations of tricalcium phosphate: 0 mM (NP), 1 mM (LP), and 2 mM (HP). Inoculation with PSB increased root, shoot and leaf biomass, and for the HP treatment, significant changes in growth patterns were observed. However, the growth responses to plant treatments tested depended on the willow species. Analysis of the leaf transcriptomes of the phosphate-solubilizing bacterium-inoculated plants showed a large variation in gene expression between the two willow species. For the Tora willow species, upregulation of genes was observed, particularly for those involved in pathways related to photosynthesis, and this effect was strongly influenced by bacterial phosphate solubilization. The Loden willow species was characterized by a general downregulation of genes involved in pathway activity that included ion transport, transcription regulation and chromosomes. The results obtained in this study provide an improved understanding of the dynamics of Salix growth and gene expression under the influence of PSB, contributing to an increase in yield and phosphorus-use efficiency.
The combined effect of fire and nitrogen addition on biodiversity and herbaceous aboveground productivity in a coastal shrubland
Authors: Qi Luyu , Song Yixin , Zhang Puyi , Sun Wenlong , Wang Wei , Yi Shijie , Li Jing , Liu Haifang , Bi Zhenggang , Du Ning , Guo Weihua
Published: August 2023

Introduction

Fire and nitrogen (N) deposition each impact biodiversity and ecosystem productivity. However, the effect of N deposition on ecosystem recovery after fire is still far from understood, especially in coastal wetlands.

Methods

We selected a typical coastal shrubland to simulate three N deposition levels (0, 10, and 20 g N m−2 year−1) under two different burned conditions (unburned and burned) in the Yellow River Delta of North China. Soil properties, soil microbial biodiversity, shrub growth parameters, herbaceous biodiversity, and aboveground productivity were determined after experimental treatments for 1 year.

Results

We found that fire had a stronger influence on the ecosystem than N addition. One year after the fire, shrub growth had significantly decreased, while soil pH, soil electrical conductivity, herbaceous biodiversity, soil microbial biodiversity, and herbaceous aboveground productivity significantly increased. Conversely, a single year of N addition only slightly increased herbaceous aboveground productivity. The combined effect of fire and N addition was only significant for fungus biodiversity and otherwise had minimal influence. Interestingly, we found that herbaceous aboveground productivity was positively associated with fungal community diversity under unburned conditions but not in burned shrublands. Fire showed a great impact on soil parameters and biodiversity in the coastal wetland ecosystem even after a full year of recovery.

Discussion

Fire may also diminish the influence of several belowground factors on herbaceous aboveground productivity, which ultimately reduces recovery and stability. Appropriate N addition may be an effective way to improve the ecosystem productivity in a wetland dominated by shrub species.
Comprehensive comparison of different parts of Paeonia ostii, a food-medicine plant, based on untargeted metabolomics, quantitative analysis, and bioactivity analysis
Authors: Zheng Yaping , Li Pei , Shen Jie , Yang Kailin , Wu Xinyan , Wang Yue , Yuan Yu-he , Xiao Peigen , He Chunnian
Published: August 2023

Introduction

Paeonia ostii T. Hong & J.X. Zhang (s.s.) (Chinese name, Fengdan) is a widely cultivated food-medicine plant in China, in which root bark, seed kernels, and flowers are utilized for their medicinal and edible values. However, other parts of the plant are not used efficiently, in part due to a poor understanding of their chemical composition and potential biological activity.

Methods

Untargeted ultra-performance liquid chromatography–quadrupole time of flight–mass spectrometry (UPLC-Q-TOF-MS) metabolomics was applied to characterize the metabolic profiles of 10 different parts of P. ostii.

Results and discussion

A total of 160 metabolites were alternatively identified definitely or tentatively, which were significantly different in various plant parts by multivariate statistical analysis. Quantitative analysis showed that underutilized plant parts also contain many active ingredients. Compared with the medicinal part of root bark, the root core part still contains a higher content of paeoniflorin (17.60 ± 0.06 mg/g) and PGG (15.50 ± 2.00 mg/g). Petals, as an edible part, contain high levels of quercitrin, and stamens have higher methyl gallate and PGG. Unexpectedly, the ovary has the highest content of methyl gallate and rather high levels of PGG (38.14 ± 1.27 mg/g), and it also contains surprisingly high concentrations of floralalbiflorin I. Paeoniflorin (38.68 ± 0.76 mg/g) is the most abundant in leaves, and the content is even higher than in the root bark. Branches are also rich in a variety of catechin derivatives and active ingredients such as hydrolyzable tannins. Seed kernels also contain fairly high levels of paeoniflorin and albiflorin. Fruit shells still contain a variety of components, although not at high levels. Seed coats, as by-products removed from peony seeds before oil extraction, have high contents of stilbenes, such as trans-gnetin H and suffruticosol B, showing significant potential for exploitation. Except for the seed kernels, extracts obtained from other parts exhibited good antioxidant activity in DPPH, ABTS, and ferric ion reducing antioxidant power (FRAP) assays (0.09–1.52 mmol TE/g). Five compounds (gallic acid, PGG, trans-resveratrol, kaempferol, and quercitrin) were important ingredients that contributed to their antioxidant activities. Furthermore, P. ostii seed cakes were first reported to possess agonistic activity toward CB1/CB2 receptors. This study provides a scientific basis for the further development and utilization of P. ostii plant resources.
Profiling the barriers to the spreading of news using news headlines
Authors: Sittar Abdul , Mladenić Dunja , Grobelnik Marko
Published: August 2023

News headlines can be a good data source for detecting the barriers to the spreading of news in news media, which can be useful in many real-world applications. In this study, we utilize semantic knowledge through the inference-based model COMET and the sentiments of news headlines for barrier classification. We consider five barriers, including cultural, economic, political, linguistic, and geographical and different types of news headlines, including health, sports, science, recreation, games, homes, society, shopping, computers, and business. To that end, we collect and label the news headlines automatically for the barriers using the metadata of news publishers. Then, we utilize the extracted common-sense inferences and sentiments as features to detect the barriers to the spreading of news. We compare our approach to the classical text classification methods, deep learning, and transformer-based methods. The results show that (1) the inference-based semantic knowledge provides distinguishable inferences across the 10 categories that can increase the effectiveness and enhance the speed of the classification model; (2) the news of positive sentiments cross the political barrier, whereas the news of negative sentiments cross the cultural, economic, linguistic, and geographical barriers; (3) the proposed approach using inferences-based semantic knowledge and sentiment improves performance compared with using only headlines in barrier classification. The average F1-score for 4 out of 5 barriers has significantly improved as follows: for cultural barriers from 0.41 to 0.47, for economic barriers from 0.39 to 0.55, for political barriers from 0.59 to 0.70 and for geographical barriers from 0.59 to 0.76.
Dark citations to Federal resources and their contribution to the public health literature
Authors: Keralis Jessica M. , Albertorio-Díaz Juan , Hoppe Travis
Published: August 2023

The term “dark citations,” which has been previously used to refer to citations of information products outside of traditional peer-reviewed journal articles, is adapted here to refer to those that are not linked to a known indexed identifier and are effectively invisible to traditional bibliometric analysis. We investigate an unexplored source of citations in the biomedical and public health literature by surveying the extent of dark citations across the U.S. government. We systematically focus on public health, quantify their occurrences across the government, and provide a comprehensive dataset for all dark citations within PubMed.
The experimental investigation of foot slip-turning motion of the musculoskeletal robot on toe joints
Authors: Nipatphonsakun Kawinna , Kawasetsu Takumi , Hosoda Koh
Published: August 2023

Owing to their complex structural design and control system, musculoskeletal robots struggle to execute complicated tasks such as turning with their limited range of motion. This study investigates the utilization of passive toe joints in the foot slip-turning motion of a musculoskeletal robot to turn on its toes with minimum movements to reach the desired angle while increasing the turning angle and its range of mobility. The different conditions of plantar intrinsic muscles (PIM) were also studied in the experiment to investigate the effect of actively controlling the stiffness of toe joints. The results show that the usage of toe joints reduced frictional torque and improved rotational angle. Meanwhile, the results of the toe-lifting angle show that the usage of PIM could contribute to preventing over-dorsiflexion of toes and possibly improving postural stability. Lastly, the results of ground reaction force show that the foot with different stiffness can affect the curve pattern. These findings contribute to the implementations of biological features and utilize them in bipedal robots to simplify their motions, and improve adaptability, regardless of their complex structure.
Poo is Precious
Authors: Kilbane John J. , Roubik Hynek , Kovacs Andras J. , Keshinro Taobat , Patel Maulik , Feijter Jacob de
Published: August 2023

Human poo contains precious nutrients, but we flush it down the drain to become wastewater. Wastewater often pollutes rivers, lakes, or the ocean. The high levels of nutrients in wastewater, primarily from human poo and pee, can decrease the amount of oxygen in the ocean, killing the fish that we eat along with other organisms. In the old days, poo from humans and animals was used on farms, as fertilizer. But this is not a practical option for the large volumes of wastewater produced in cities. What if the nutrients from wastewater could be used to solve rather than to create environmental problems? Using single-celled, water-dwelling plants called microalgae to treat wastewater has many benefits. Clean water helps everyone. Recycling nutrients from wastewater and using them as fertilizers will help farmers. Also, useful products like fuels and plastics can be made from these algae. New and cheaper wastewater treatment technologies are needed to create a better future. You could be part of the solution!
Role of farmers’ entrepreneurial orientation, women’s participation, and information and communication technology use in responsible farm production: a step towards sustainable food production
Authors: Shahbaz Pomi , Haq Shamsheerul , Abbas Azhar , Azadi Hossein , Boz Ismet , Yu Mark , Watson Susan
Published: August 2023

Responsible production is essential for sustainable development and for ensuring global food security. The concept of responsible production has been well studied in other sectors of the economy, but has yet to gain recognition in the agricultural sector. Therefore, this study examined responsible production in the context of agriculture and the factors affecting responsible farm production in the developing country of Pakistan. Face-to-face interviews were conducted to collect data from 196 farmers selected using the multistage random sampling method. An independent sample t-test, chi-square test, and ordered probit model were used to analyze the data. The responsible farm production index was estimated based on the climate change adaptation, resource efficiency, carbon footprints, and economic returns of each farm. The mean value of the responsible farm production index is 0.69. The farmers were divided into low-, moderate-, and highly responsible farm producers using cluster analysis. More than 36% of farms were highly responsible. The results revealed that women’s participation in farming activities, extension services, the use of information and communication technologies, and farmer entrepreneurial orientation dimensions significantly affected responsible farm production. Farm producers using the Internet for agriculture had a 1.4% points higher probability of belonging to the highly responsible farm producer category compared to those who did not use the Internet to obtain agricultural information. Farms with women’s participation in agricultural activities were 33.5% points more likely to belong to the highly responsible farm producer category than farms where only males perform agricultural operations. Therefore, women’s empowerment and farmers’ entrepreneurial skills are absolute necessities of responsible farming. This study piques the interests of stakeholders while also adding to the scant body of knowledge on responsible farm production around the world. Furthermore, this study is critical for developing a roadmap for long-term sustainable agricultural development.
Challenges and Opportunities Associated With Drug Delivery for the Treatment of Solid Tumors
Authors: Paresishvili Teona , Kakabadze Zurab
Published: August 2023

In this review, we discuss the effectiveness of drug delivery system based on metal nanoparticles, and also, describe the problems associated with their delivery to tumor cells. Throughout recent years, more reports have appeared in the literature that demonstrate promising results for the treatment of various types of cancer using metal-based nanoparticles. Due to their unique physical and chemical properties, metal nanoparticles are effectively being used for the delivery of drug to the tumor cells, for cancer diagnosis and treatment. They can also be synthesized allowing the control of size and shape. However, the effectiveness of the metal nanoparticles for cancer treatment largely depends on their stability, biocompatibility, and ability to selectively affect tumor cells after their systemic or local administration. Another major problem associated with metal nanoparticles is their ability to overcome tumor tissue barriers such as atypical blood vessel structure, dense and rigid extracellular matrix, and high pressure of tumor interstitial fluid. The review also describes the design of tumor drug delivery systems that are based on metal nanoparticles. The mechanism of action of metal nanoparticles on cancer cells is also discussed. Considering the therapeutic safety and toxicity of metal nanoparticles, the prospects for their use for future clinical applications are being currently reviewed.