bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of trehalolipid biosurfactant produced by the novel marine strain Rhodococcus sp. SP1d and its potential for environmental applications
Authors: Andreolli Marco , Villanova Valeria , Zanzoni Serena , D’Onofrio Mariapina , Vallini Giovanni , Secchi Nicola , Lampis Silvia
Published: July 2023

Background

Biosurfactants are surface-active compounds with environmental and industrial applications. These molecules show higher biocompatibility, stability and efficiency compared to synthetic surfactants. On the other hand, biosurfactants are not cost-competitive to their chemical counterparts. Cost effective technology such as the use of low-cost substrates is a promising approach aimed at reducing the production cost. This study aimed to evaluate the biosurfactant production and activity by the novel strain Rhodococcus sp. SP1d by using different growth substrates. Therefore, to exploit the biosurfactant synthesized by SP1d for environmental applications, the effect of this compound on the bacteria biofilm formation was evaluated. Eventually, for a possible bioremediation application, the biosurfactant properties and its chemical characteristics were investigated using diesel as source of carbon.

Results

Rhodococcus sp. SP1d evidence the highest similarity to Rhodococcus globerulus DSM 43954T and the ability to biosynthesize surfactants using a wide range of substrates such as exhausted vegetable oil, mineral oil, butter, n-hexadecane, and diesel. The maximum production of crude biosurfactant after 10 days of incubation was reached on n-hexadecane and diesel with a final yield of 2.38 ± 0.51 and 1.86 ± 0.31 g L− 1 respectively. Biosurfactants produced by SP1d enhanced the biofilm production of P. protegens MP12. Moreover, the results showed the ability of SP1d to produce biosurfactants on diesel even when grown at 10 and 18 °C. The biosurfactant activity was maintained over a wide range of NaCl concentration, pH, and temperature. A concentration of 1000 mg L− 1 of the crude biosurfactant showed an emulsification activity of 55% towards both xylene and olive oil and a reduction of 25.0 mN m− 1 of surface tension of water. Eventually, nuclear magnetic resonance spectroscopy indicated that the biosurfactant is formed by trehalolipids.

Conclusions

The use of low-cost substrates such as exhausted oils and waste butter reduce both the costs of biosurfactant synthesis and the environmental pollution due to the inappropriate disposal of these residues. High production yields, stability and emulsification properties using diesel and n-hexadecane as substrates, make the biosurfactant produced by SP1d a sustainable biocompound for bioremediation purpose. Eventually, the purified biosurfactant improved the biofilm formation of the fungal antagonistic strain P. protegens MP12, and thus seem to be exploitable to increase the adherence and colonization of plant surfaces by this antagonistic strain and possibly enhance antifungal activity.
Genetic inactivation of the Carnitine/Acetyl-Carnitine mitochondrial carrier of Yarrowia lipolytica leads to enhanced odd-chain fatty acid production
Authors: Messina Eugenia , de Souza Camilla Pires , Cappella Claudia , Barile Simona Nicole , Scarcia Pasquale , Pisano Isabella , Palmieri Luigi , Nicaud Jean-Marc , Agrimi Gennaro
Published: July 2023

Background

Mitochondrial carriers (MCs) can deeply affect the intracellular flux distribution of metabolic pathways. The manipulation of their expression level, to redirect the flux toward the production of a molecule of interest, is an attractive target for the metabolic engineering of eukaryotic microorganisms. The non-conventional yeast Yarrowia lipolytica is able to use a wide range of substrates. As oleaginous yeast, it directs most of the acetyl-CoA therefrom generated towards the synthesis of lipids, which occurs in the cytoplasm. Among them, the odd-chain fatty acids (OCFAs) are promising microbial-based compounds with several applications in the medical, cosmetic, chemical and agricultural industries.

Results

In this study, we have identified the MC involved in the Carnitine/Acetyl-Carnitine shuttle in Y. lipolytica, YlCrc1. The Y. lipolytica Ylcrc1 knock-out strain failed to grow on ethanol, acetate and oleic acid, demonstrating the fundamental role of this MC in the transport of acetyl-CoA from peroxisomes and cytoplasm into mitochondria. A metabolic engineering strategy involving the deletion of YlCRC1, and the recombinant expression of propionyl-CoA transferase from Ralstonia eutropha (RePCT), improved propionate utilization and its conversion into OCFAs. These genetic modifications and a lipogenic medium supplemented with glucose and propionate as the sole carbon sources, led to enhanced accumulation of OCFAs in Y. lipolytica.

Conclusions

The Carnitine/Acetyl-Carnitine shuttle of Y. lipolytica involving YlCrc1, is the sole pathway for transporting peroxisomal or cytosolic acetyl-CoA to mitochondria. Manipulation of this carrier can be a promising target for metabolic engineering approaches involving cytosolic acetyl-CoA, as demonstrated by the effect of YlCRC1 deletion on OCFAs synthesis.
The mediating role of HbA1c in the association between elevated low-density lipoprotein cholesterol levels and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus
Authors: Zhang Hui , Chen Yang , Zhu Wenwen , Niu Tong , Song Bing , Wang Hongxiao , Wang Wei , Zhang Haoqiang
Published: July 2023

Background

Increased levels of low-density lipoprotein cholesterol (LDL-C) have been identified as one potential risk factor for diabetic peripheral neuropathy (DPN) in patients. The current study seeks to clarify the link between LDL-C, hyperglycemia, and DPN in patients with type 2 diabetes mellitus (T2DM).

Methods

Here, a total of 120 T2DM individuals were recruited. These volunteers with T2DM were divided into 2 groups, based on the presence or absence of peripheral neuropathy. Additionally, their baseline characteristics were compared. Association among LDL-C and glycosylated hemoglobin (HbA1c) levels and DPN, particularly with respect to specific nerve conduction velocity were analyzed. To identify factors influencing DPN, regression was performed. Furthermore, mediation analysis was employed to evaluate the indirect, direct and total effects of LDL-C on specific nerve conduction velocity, with HbA1c serving as a mediator.

Results

Compared to 55 patients without DPN, 65 patients with DPN demonstrated elevated levels of LDL-C and HbA1c. Both LDL-C and HbA1c have been found to be associated with reduced the motor fiber conduction velocities of Ulnar (or the Common peroneal) nerve in diabetic patients. HbA1c is one of the known risk factors for DPN in individuals with T2DM. Further mediation analysis revealed that the effect of LDL-C on the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities are fully mediated by HbA1c in patients with T2DM.

Conclusions

The impact of elevated LDL-C levels upon the Ulnar (or the Common peroneal) nerve motor fiber conduction velocities in patients with T2DM was found to be entirely mediated by increased HbA1c levels.
The role of onsite Implanon insertion training for HEWs for sustainable FP programs in Ethiopia: a mixed-method study
Authors: Tilahun Yewondwossen , Belayihun Bekele , Teshome Luwam , Zerihun Habtamu , Asnake Mengistu
Published: July 2023

Background

Training health extension workers on Implanon insertion offsite, or away from the workplace, can be cost-intensive, can depend on the human and financial resources of partners, and can compromise routine health services by taking health workers off the job. To address these limitations, the USAID Transform Primary Health Care Activity in Ethiopia designed an onsite Implanon insertion training at the primary health care level. This study compared and documented the implementation experience of onsite vs offsite Implanon insertion training for health extension workers.

Methods

In a mixed-method study conducted in March 2020, the team collected training data from 468 participants—half trained onsite and half offsite—and conducted key informant interviews with 20 purposively sampled individuals. The team analyzed this data, summarizing the data in tables and figures and performing a t test with p value < 0.05 using SPSS v.20. Qualitative data were analyzed manually in Excel and summarized in Word based on emerging themes.

Results

Health extension workers trained onsite were away from routine work an average of 3 days compared to 8 days for those trained offsite (P < 0.001). The difference in average per-trainee cost of onsite (2707 Birr = 87.3 USD) and offsite (6006 Birr = 193.7USD) training was significant (P < 0.001). There was no significant difference in mean scores of onsite and offsite trainees on the knowledge pre-test (P < 0.947) and post-test (P < 0.220) or in simulated practice on an arm model (p < 0.202). Onsite trainees, assigned to their own health post for clinical practice, performed Implanon insertions on an average of 10 clients: offsite trainees on an average of 5 clients. Most interview participants reported that the onsite Implanon training was better organized, conducted, followed up, and monitored by health centers to ensure community-level access to Implanon services, with quality and continuity.

Conclusions

Onsite training is a promising approach and minimizes service interruption. It is a likely strategy for on-demand training of health extension workers and immediate assignment of skilled providers to ensure access to and continuity of quality community-level Implanon care.

Trial registration N/A.
A 90-day oral exposure to food-grade gold at relevant human doses impacts the gut microbiota and the local immune system in a sex-dependent manner in mice
Authors: Evariste Lauris , Lamas Bruno , Ellero-Simatos Sandrine , Khoury Laure , Cartier Christel , Gaultier Eric , Chassaing Benoit , Feltin Nicolas , Devoille Laurent , Favre Georges , Audebert Marc , Houdeau Eric
Published: July 2023

Background

Edible gold (Au) is commonly used as a food additive (E175 in EU) for confectionery and cake decorations, coatings and in beverages. Food-grade gold is most often composed of thin Au sheets or flakes exhibiting micro- and nanometric dimensions in their thickness. Concerns about the impact of mineral particles used as food additives on human health are increasing with respect to the particular physico-chemical properties of nanosized particles, which enable them to cross biological barriers and interact with various body cell compartments. In this study, male and female mice were exposed daily to E175 or an Au nanomaterial (Ref-Au) incorporated into food at relevant human dose for 90 days in order to determine the potential toxicity of edible gold.

Results

E175 or Ref-Au exposure in mice did not induce any histomorphological damage of the liver, spleen or intestine, nor any genotoxic effects in the colon and liver despite an apparent higher intestinal absorption level of Au particles in mice exposed to Ref-Au compared to the E175 food additive. No changes in the intestinal microbiota were reported after treatment with Ref-Au, regardless of sex. In contrast, after E175 exposure, an increase in the Firmicutes/Bacteroidetes ratio and in the abundance of Proteobacteria were observed in females, while a decrease in the production of short-chain fatty acids occurred in both sexes. Moreover, increased production of IL-6, TNFα and IL-1β was observed in the colon of female mice at the end of the 90-day exposure to E175, whereas, decreased IL-6, IL-1β, IL-17 and TGFβ levels were found in the male colon.

Conclusions

These results revealed that a 90-day exposure to E175 added to the diet alters the gut microbiota and intestinal immune response in a sex-dependent manner in mice. Within the dose range of human exposure to E175, these alterations remained low in both sexes and mostly appeared to be nontoxic. However, at the higher dose, the observed gut dysbiosis and the intestinal low-grade inflammation in female mice could favour the occurrence of metabolic disorders supporting the establishment of toxic reference values for the safe use of gold as food additive.
Associations of in-hospital postpartum feeding experiences with exclusive breastfeeding practices among infants in rural Sichuan, China
Authors: Weber Ann M. , Guo Yian , Zhang Evelyn , Gruber Susan , Medina Alexis , Zhou Huan , Darmstadt Gary L.
Published: July 2023

Background

In rural China, exclusive breastfeeding (EBF) prevalence is low and hospitals often fail to attain baby-friendly feeding objectives, such as ≥ 75% of newborns exclusively breastfed from birth to discharge. Empirical evidence for the impact of increased hospital compliance with recommended feeding guidelines on continued EBF in rural China is lacking. We sought to measure and model the association of newborns’ in-hospital feeding experiences with EBF practice in infancy to inform policies for EBF promotion.

Methods

Data were cross-sectional from 785 caregivers of infants < 6 months of age, collected from November to December 2019 in four underdeveloped counties/districts in Sichuan Province. In-hospital feeding practices were determined, and prevalence of current infant feeding practices was calculated from 24-h recall and categorized according to WHO/UNICEF Infant and Young Child Feeding categories as EBF, breastfed with non-milk liquids, mixed feeding, breastfed with solids, and not breastfed. Relative risk ratios were estimated using adjusted multinomial logistic regression to examine risk factors for non-EBF practices compared to EBF, including in-hospital feeding experiences. The regression model was used to investigate change in EBF prevalence under alternative in-hospital experiences.

Results

Only 38.1% of under-six-month-old infants were being exclusively breastfed when data were collected; 61.8% and 77.6% had been fed water and infant formula, respectively, in the hospital. Infants who were fed water or formula before discharge were estimated as 2–3 times as likely to be non-EBF than EBF up to age six months. According to our model, EBF prevalence would have increased to 53.7% (95% confidence interval (CI) 46.1, 61.2) had ≥ 75% of infants been exclusively breastfed and water-based feeds eliminated in-hospital.

Conclusions

Given the importance of infants’ first feeding experiences in the establishment and continuation of EBF, it is imperative that rural Chinese hospitals actively seek to limit infant formula feeds to medically indicated situations and eliminate water-based feeds.
Pulmonary interleukin 1 beta/serum amyloid A3 axis promotes lung metastasis of hepatocellular carcinoma by facilitating the pre-metastatic niche formation
Authors: Zhang Chong , Li Qing , Xu Qi , Dong Wei , Li Chunmei , Deng Bin , Gong Jiao , Zhang Li-Zhen , Jin Junfei
Published: July 2023

Background

Increasing evidence suggests a vital role of the pre-metastatic niche in the formation of distant metastasis of many cancers. However, how the pre-metastatic niche is formed and promotes pulmonary metastasis of hepatocellular carcinoma (HCC) remains unknown.

Methods

Orthotopic liver tumor models and RNA-Seq were used to identify dysregulated genes in the pre-metastatic lung. Il1b knockout (Il1b−/−) mice and lentivirus-mediated gene knockdown/overexpression were utilized to demonstrate the role of interleukin 1 beta (IL-1β)/serum amyloid A3 (SAA3) in the pre-metastatic niche formation and pulmonary metastasis. The potential molecular mechanisms were investigated by RNA-Seq, real-time quantitative PCR (qPCR), western blotting, immunohistochemistry (IHC), flow cytometry, luciferase reporter assay, double immunofluorescent staining and H&E staining.

Results

Accumulation of myeloid cells and upregulation of IL-1β were observed in the pre-metastatic lung of orthotopic liver tumor models. Myeloid cells accumulation and pulmonary metastasis were suppressed in Il1b−/− mice and Il1r1-silencing mice. Mechanistically, SAA3 and matrix metallopeptidase 9 (MMP9) were identified as potential downstream targets of IL-1β. Overexpression of SAA3 in the lungs of Il1b−/− mice restored myeloid cells accumulation and pulmonary metastasis of the orthotopic HCC xenografts. Moreover, alveolar macrophages-derived IL-1β dramatically enhanced SAA3 expression in alveolar epithelial cells in an NF-κB dependent manner and increased MMP9 levels in an autocrine manner. Furthermore, SAA3 recruited myeloid cells to the lung without affecting the expression of MMP9 in myeloid cells.

Conclusions

Our study suggests a key role of pulmonary IL-1β and SAA3 in creating a permissive lung pre-metastatic niche by enhancing MMP9 expression and recruiting myeloid cells, respectively, thus promoting pulmonary metastasis of HCC.
Effects of intraoperative inspired oxygen fraction (FiO2 0.3 vs 0.8) on patients undergoing off-pump coronary artery bypass grafting: the CARROT multicenter, cluster-randomized trial
Authors: Nam Karam , Nam Jae-Sik , Kim Hye-Bin , Chung Jaeyeon , Hwang In Eob , Ju Jae-Woo , Bae Jinyoung , Lee Seohee , Cho Youn Joung , Shim Jae-Kwang , Kwak Young-Lan , Chin Ji-Hyun , Choi In-Cheol ,   for the CARdiac suRgery and Oxygen Therapy (CARROT) Investigators, Lee Eun-Ho , Jeon Yunseok
Published: July 2023

Background

To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB).

Methods

This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared.

Results

A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83–1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18–3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002).

Conclusions

In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB.

Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019).
Clinical utility of a novel test for assessing cardiovascular disease risk in type 2 diabetes: a randomized controlled trial
Authors: Peabody John W. , Paculdo David , de Belen Enrico , Ganesan Divya , Cooney Isabella , Trujillo Nelson
Published: July 2023

Background

The risk for and treatment of cardiovascular disease (CVD) in type 2 diabetes (T2DM) is often incorrect and delayed. We wished to determine if a novel test improved physicians’ ability to risk stratify, diagnose, and treat patients with T2DM.

Methods

In a 2-phase randomized controlled trial comparing the clinical workup, diagnosis, and management of online, simulated patients with T2DM in a nationwide sample of cardiologists and primary care physicians, participants were randomly assigned to control or one of two intervention groups. Intervention participants had access to standard of care diagnostic tools plus a novel diagnostic CVD risk stratification test.

Results

In control, there was no change in CV risk stratification of simulated patients between baseline and round 2 (37.1 to 38.3%, p = 0.778). Pre-post analysis showed significant improvements in risk stratification in both Intervention 1 (38.7 to 65.3%) and Intervention 2 (41.9 to 65.8%) (p < 0.01) compared to controls. Both intervention groups significantly increased prescribing SGLT2 inhibitors/GLP1 receptor agonists versus control, + 18.9% for Intervention 1 (p = 0.020) and 1 + 9.4% for Intervention 2 (p = 0.014). Non-pharmacologic treatment improved significantly compared to control (+ 30.0% in Intervention 1 (p < 0.001) and + 22.8% in Intervention 2 (p = 0.001). Finally, monitoring HgbA1C, blood pressure, and follow-up visit frequency improved by + 20.3% (p = 0.004) in Intervention 1 and + 29.8% (p < 0.001) in Intervention 2 compared with control.

Conclusion

Use of the novel test significantly improved CV risk stratification among T2DM patients. Statistically significant increases treatments were demonstrated, specifically SGLT2 inhibitors and GLP1 receptor antagonists and recommendations of evidence-based non-pharmacologic treatments.

Trial registration ClinicalTrials.gov, NCT05237271
Successful treatment with doxycycline monotherapy for human infection with Babesia venatorum (Babesiidae, Sporozoa) in China: a case report and proposal for a clinical regimen
Authors: Huang Lei , Sun Yi , Huo Dan-Dan , Xu Ming , Xia Luo-Yuan , Yang Ning , Hong Wei , Huang Lin , Nie Wei-Min , Liao Ru-He , Zhang Ming-Zhu , Zhu Dai-Yun , Li Yan , Ma He-Cheng , Zhang Xin , Li Yong-Gang , Huang Xin-An , Wang Jing-Yuan , Cao Wu-Chun , Wang Fu-Sheng , Jiang Jia-Fu
Published: July 2023

Background

Human babesiosis is a worldwide disease caused by intraerythrocytic protozoa of the genus Babesia. It is transmitted by bites from ixodid ticks, and mechanically transmitted by blood transfusion. It is primarily treated with quinine and/or atovaquone, which are not readily available in China. In this study, we developed a novel treatment regimen involving doxycycline monotherapy in a patient with severe Babesia venatorum infection as an alternative therapeutic medication. The aim of our study is to provide a guidance for clinical practice treatment of human babesiosis.

Case presentation

A 73-year-old man who had undergone splenectomy and blood transfusion 8 years prior, presented with an unexplained fever, headache, and thrombocytopenia, and was admitted to the Fifth Medical Center of the PLA General Hospital. He was diagnosed with B. venatorum infection by morphological review of thin peripheral blood smears, which was confirmed by multi-gene polymerase chain reaction (PCR), and sequencing of the entire 18s rRNA and partial β-tubulin encoding genes, as well as isolation by animal inoculation. The doxycycline monotherapy regimen (peros, 0.1 g bisindie) was administered following pharmacological guidance and an effective outcome was observed. The patient recovered rapidly following the doxycycline monotherapy. The protozoan load in peripheral blood samples decreased by 88% in hematocrit counts after 8 days, and negative PCR results were obtained after 90 days of follow-up at the hospital. The treatment lasted for 3 months without any side effects or sequelae. The nine-month follow-up survey of the patient did not reveal any signs of recrudescence or anti-babesial tolerance.

Conclusions

We have reported a clinical case of successful doxycycline monotherapy for human babesiosis caused by B. venatorum, which provides an optional medical intervention for human babesiosis.

Graphical Abstract
A closed-loop ventilation mode that targets the lowest work and force of breathing reduces the transpulmonary driving pressure in patients with moderate-to-severe ARDS
Authors: Buiteman-Kruizinga Laura A. , van Meenen David M. P. , Bos Lieuwe D. J. , van der Heiden Pim L. J. , Paulus Frederique , Schultz Marcus J.
Published: July 2023

Introduction

The driving pressure (ΔP) has an independent association with outcome in patients with acute respiratory distress syndrome (ARDS). INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop mode of ventilation that targets the lowest work and force of breathing.

Aim

To compare transpulmonary and respiratory system ΔP between closed-loop ventilation and conventional pressure controlled ventilation in patients with moderate-to-severe ARDS.

Methods

Single-center randomized cross-over clinical trial in patients in the early phase of ARDS. Patients were randomly assigned to start with a 4-h period of closed-loop ventilation or conventional ventilation, after which the alternate ventilation mode was selected. The primary outcome was the transpulmonary ΔP; secondary outcomes included respiratory system ΔP, and other key parameters of ventilation.

Results

Thirteen patients were included, and all had fully analyzable data sets. Compared to conventional ventilation, with closed-loop ventilation the median transpulmonary ΔP with was lower (7.0 [5.0–10.0] vs. 10.0 [8.0–11.0] cmH2O, mean difference − 2.5 [95% CI − 2.6 to − 2.1] cmH2O; P = 0.0001). Inspiratory transpulmonary pressure and the respiratory rate were also lower. Tidal volume, however, was higher with closed-loop ventilation, but stayed below generally accepted safety cutoffs in the majority of patients.

Conclusions

In this small physiological study, when compared to conventional pressure controlled ventilation INTELLiVENT-ASV reduced the transpulmonary ΔP in patients in the early phase of moderate-to-severe ARDS. This closed-loop ventilation mode also led to a lower inspiratory transpulmonary pressure and a lower respiratory rate, thereby reducing the intensity of ventilation.

Trial registration Clinicaltrials.gov, NCT03211494, July 7, 2017. https://clinicaltrials.gov/ct2/show/NCT03211494?term=airdrop&draw=2&rank=1.
Assembly processes and functional diversity of marine protists and their rare biosphere
Authors: Ramond Pierre , Siano Raffaele , Sourisseau Marc , Logares Ramiro
Published: July 2023

Background

The mechanisms shaping the rare microbial biosphere and its role in ecosystems remain unclear. We developed an approach to study ecological patterns in the rare biosphere and use it on a vast collection of marine microbiomes, sampled in coastal ecosystems at a regional scale. We study the assembly processes, and the ecological strategies constituting the rare protistan biosphere. Using the phylogeny and morpho-trophic traits of these protists, we also explore their functional potential.

Results

Taxonomic community composition remained stable along rank abundance curves. Conditionally rare taxa, driven by selection processes, and transiently rare taxa, with stochastic distributions, were evidenced along the rank abundance curves of all size-fractions. Specific taxa within the divisions Sagenista, Picozoa, Telonemia, and Choanoflagellida were rare across time and space. The distribution of traits along rank abundance curves outlined a high functional redundancy between rare and abundant protists. Nevertheless, trophic traits illustrated an interplay between the trophic groups of different size-fractions.

Conclusions

Our results suggest that rare and abundant protists are evolutionary closely related, most notably due to the high microdiversity found in the rare biosphere. We evidenced a succession of assembly processes and strategies of rarity along rank abundance curves that we hypothesize to be common to most microbiomes at the regional scale. Despite high functional redundancy in the rare protistan biosphere, permanently rare protists were evidenced, and they could play critical functions as bacterivores and decomposers from within the rare biosphere. Finally, changes in the composition of the rare protistan biosphere could be influenced by the trophic regime of aquatic ecosystems. Our work contributes to understanding the role of rare protists in microbiomes.
Emerging nano-scale delivery systems for the treatment of osteoporosis
Authors: Dayanandan Anoop Puthiyoth , Cho Woong Jin , Kang Hyemin , Bello Alvin Bacero , Kim Byoung Ju , Arai Yoshie , Lee Soo-Hong
Published: July 2023

Osteoporosis is a pathological condition characterized by an accelerated bone resorption rate, resulting in decreased bone density and increased susceptibility to fractures, particularly among the elderly population. While conventional treatments for osteoporosis have shown efficacy, they are associated with certain limitations, including limited drug bioavailability, non-specific administration, and the occurrence of adverse effects. In recent years, nanoparticle-based drug delivery systems have emerged as a promising approach for managing osteoporosis. Nanoparticles possess unique physicochemical properties, such as a small size, large surface area-to-volume ratio, and tunable surface characteristics, which enable them to overcome the limitations of conventional therapies. These nanoparticles offer several advantages, including enhanced drug stability, controlled release kinetics, targeted bone tissue delivery, and improved drug bioavailability. This comprehensive review aims to provide insights into the recent advancements in nanoparticle-based therapy for osteoporosis. It elucidates the various types of nanoparticles employed in this context, including silica, polymeric, solid lipid, and metallic nanoparticles, along with their specific processing techniques and inherent properties that render them suitable as potential drug carriers for osteoporosis treatment. Furthermore, this review discusses the challenges and future suggestions associated with the development and translation of nanoparticle drug delivery systems for clinical use. These challenges encompass issues such as scalability, safety assessment, and regulatory considerations. However, despite these challenges, the utilization of nanoparticle-based drug delivery systems holds immense promise in revolutionizing the field of osteoporosis management by enabling more effective and targeted therapies, ultimately leading to improved patient outcomes.
Design, printing optimization, and material testing of a 3D-printed nasal osteotomy task trainer
Authors: Schlegel Lauren , Malani Eric , Belko Sara , Kumar Ayan , Barbarite Eric , Krein Howard , Heffelfinger Ryan , Hutchinson Morgan , Pugliese Robert
Published: July 2023

Background

For difficult or rare procedures, simulation offers an opportunity to provide education and training. In developing an adequate model to utilize in simulation, 3D printing has emerged as a useful technology to provide detailed, accessible, and high-fidelity models. Nasal osteotomy is an essential step in many rhinoplasty surgeries, yet it can be challenging to perform and difficult to receive adequate exposure to this nuanced portion of the procedure. As it currently stands, there are limited opportunities to practice nasal osteotomy due to the reliance on cadaveric bones, which are expensive, difficult to obtain, and require appropriate facilities and personnel. While previous designs have been developed, these models leave room for improvement in printing efficiency, cost, and material performance. This manuscript aims to describe the methodology for the design of an updated nasal osteotomy training model derived from anatomic data and optimized for printability, usability, and fidelity. Additionally, an analysis of multiple commercially available 3D printing materials and technologies was conducted to determine which offered superior equivalency to bone.

Methods

This model was updated from a first-generation model previously described to include a more usable base and form, reduce irrelevant structures, and optimize geometry for 3D printing, while maintaining the nasal bones with added stabilizers essential for function and fidelity. For the material comparison, this updated model was printed in five materials: Ultimaker Polylactic Acid, 3D Printlife ALGA, 3DXTECH SimuBone, FibreTuff, and FormLabs Durable V2. Facial plastic surgeons tested the models in a blinded, randomized fashion and completed surveys assessing tactile feedback, audio feedback, material limitation, and overall value.

Results

A model optimizing printability while maintaining quality in the area of interest was developed. In the material comparison, SimuBone emerged as the top choice amongst the evaluating physicians in an experience-based subjective comparison to human bone during a simulated osteotomy procedure using the updated model.

Conclusion

The updated midface model that was user-centered, low-cost, and printable was designed. In material testing, Simubone was rated above other materials to have a more realistic feel.
Feasibility of manufacture of chimeric antigen receptor-regulatory T cells from patients with end-stage renal disease
Authors: Bastian Hervé , Lounnas-Mourey Nadia , Heimendinger Pierre , Hsu Benjamin L. , Schreeb Katharina H. , Chapman Claire , Culme-Seymour Emily , Atkinson Gillian F. , Cantarovich Diego
Published: July 2023

Background

Gene-modified cell therapy with regulatory T cells (Tregs) is a promising approach to prevent graft rejection and induce immunological tolerance in organ transplantation. We are developing a cell therapy comprising autologous naïve Tregs that are isolated from leukapheresate, transduced with lentiviral vector encoding a chimeric antigen receptor (CAR) recognising human leukocyte antigen class I molecule A*02 (HLA-A*02), and expanded ex vivo before cryopreservation as resultant drug product (TX200-TR101). In an ongoing first-in-human study (NCT04817774), kidney transplant recipients will receive a single infusion of TX200-TR101 2–3 months after transplantation. The phase 0 study described here evaluated the feasibility of manufacture of TX200-TR101 for the target population, i.e., end-stage renal disease (ESRD) necessitating kidney transplantation. Participants in this study did not receive an infusion of drug product.

Methods

Four patients with ESRD and HLA-A*02 negative typing underwent leukapheresis to collect starting material for manufacture of TX200-TR101. Manufacturing success criteria were predefined as a batch of CAR-Tregs with cell quantity in each batch ≥ 104 cells/kg body weight, cell viability ≥ 70%, transduction efficiency ≥ 20% and hypomethylation of the FoxP3 gene (Treg-specific demethylated region [TSDR]) ≥ 80%. Other manufacturing variables included Treg identity and maturation by phenotyping, residual bead count, vector copy number, endotoxin level, sterility, and presence of mycoplasma. The characteristics of leukapheresate starting material and drug product from patients with ESRD were compared with those from commercially purchased leukapheresate from 10 healthy donors.

Results

No safety issues were identified during leukapheresis collections. Batches of drug product were manufactured from all 4 patients with ESRD and met the predefined success criteria. There was some variability in leukapheresate starting material in terms of volume of apheresis and total leukocyte counts between patients with ESRD and healthy donors, but percentage differential white blood cell counts were comparable. The quality, quantity and functional activity of manufactured CAR-Tregs were similar between ESRD patients and healthy donors. CAR-Treg drug product from one patient with pre-existing lymphopenia had similar high quality but reduced cell quantity compared with batches from the other patients with ESRD, although yield was still above the predefined target minimum number of cells.

Conclusions

Manufacture of high-quality naïve CAR-Tregs from patients with ESRD is safe and feasible.
Fever in the initial stage of IIM patients: an early clinical warning sign for AE-ILD
Authors: Liu Ting , Chen Haifeng , Shi Yitian , Xu Wei , Yuan Fenghong
Published: July 2023

Background

Fever is a common symptom of Idiopathic inflammatory myopathies (IIM). However, the exact correlation between fever and the prognosis of IIM is still unclear. This study aims to clarify if the IIM patients initiated with fever are associated with poorer outcomes.

Methods

This was a single-center retrospective cohort study. Data were collected from 79 newly diagnosed, treatment-naive IIM patients in the Affiliated Wuxi People’s Hospital of Nanjing Medical University (Wuxi, Jiangsu, China) from November 2016 to June 2020. According to the presence or absence of fever at the onset, the IIM patients were divided into two groups(fever group n = 28, without fever group n = 51) Clinical characteristics, laboratory data, treatment, and outcomes were recorded. The Kaplan-Meier and log-rank tests were used to compare the all-cause mortality, relapse rate, and acute exacerbation of interstitial lung disease (AE-ILD) incidence. The association of fever with the outcomes was assessed in the unadjusted and adjusted forward logistic regression model.

Results

Compared with the non-fever group, the age at onset of the fever group was higher, and mechanic’s hands (MH) and interstitial lung disease (ILD) were more common. Systemic inflammation (CRP and ESR) was significantly higher in the fever group, while the level of albumin(ALB) and muscle enzymes were lower. The fever group seemed to be received more aggressive treatment, with higher dose glucocorticoids and higher rates of intravenous immunoglobulins(IVIG) use. The all-cause mortality rate and the incidence rate of AE-ILD were higher in the fever group. Even adjusted for the age at onset and treatments, fever was significantly associated with AE-ILD and all-cause mortality.

Conclusion

Our study has demonstrated that fever at initial diagnosis is associated with AE-ILD and mortality. Fever should serve as an early clinical warning sign for poor outcomes in IIM patients.
Derivation and validation of a screening tool for stroke-associated sepsis
Authors: Stösser Sebastian , Kleusch Lisa , Schenk Alina , Schmid Matthias , Petzold Gabor C.
Published: July 2023

Background

Post-stroke infections may cause sepsis, which is associated with poor clinical outcome. Sepsis is defined by life-threatening organ dysfunction that can be identified using the Sequential Organ Failure Assessment (SOFA) score. The applicability of the SOFA score for patients not treated on an intensive care unit (ICU) is limited. The aim of this study was to develop and validate an easier-to-use modification of the SOFA score for stroke patients.

Methods

Using a registry-based cohort of 212 patients with large vessel occlusion stroke and infection, potential predictors of a poor outcome indicating sepsis were assessed by logistic regression. The derived score was validated on a separate cohort of 391 patients with ischemic stroke and infection admitted to our hospital over a period of 1.5 years.

Results

The derived Stroke-SOFA (S-SOFA) score included the following predictors: National Institutes of Health stroke scale ≥ 14, peripheral oxygen saturation < 90%, mean arterial pressure < 70 mmHg, thrombocyte count < 150 109/l and creatinine ≥ 1.2 mg/dl. The area under the receiver operating curve for the prediction of a poor outcome indicating sepsis was 0.713 [95% confidence interval: 0.665–0.762] for the S-SOFA score, which was comparable to the standard SOFA score (0.750 [0.703–0.798]), but the prespecified criteria for non-inferiority were not met (p = 0.115). However, the S-SOFA score was non-inferior compared to the SOFA score in non-ICU patients (p = 0.013).

Conclusions

The derived S-SOFA score may be useful to identify non-ICU patients with stroke-associated sepsis who have a high risk of a poor outcome.
Explainable machine learning for hydrocarbon prospect risking
Authors: Mustafa Ahmad , Koster Klaas , AlRegib Ghassan
Published: July 2023

Hydrocarbon prospect risk assessment is an important process in oil and gas exploration involving the integrated analysis of various geophysical data modalities, including seismic data, well logs, and geologic information, to estimate the likelihood of drilling success for a given drill location. Over the years, geophysicists have attempted to understand the various factors at play influencing the probability of success for hydrocarbon prospects. Toward this end, a large database of prospect drill outcomes and associated attributes has been collected and analyzed via correlation-based techniques to determine the features that contribute the most in deciding the final outcome. Machine learning (ML) has the potential to model complex feature interactions to learn input-output mappings for complicated high-dimensional data sets. However, in many instances, ML models are not interpretable to end users, limiting their utility toward understanding the underlying scientific principles for the problem domain and being deployed to assist in the risk assessment process. In this context, we leverage the concept of explainable ML to interpret various black-box ML models trained on the aforementioned prospect database for risk assessment. Using various case studies on real data, we determine that this model-agnostic explainability analysis for prospect risking can (1) reveal novel scientific insights into the interplay of various features in regard to deciding prospect outcome, (2) assist with performing feature engineering for ML models, (3) detect bias in data sets involving spurious correlations, and (4) build a global picture of a model’s understanding of the data by aggregating local explanations on individual data points.
Three Cases of Non-islet Cell Tumor Hypoglycemia Highlighting Efficacy of Glucocorticoid Treatment
Authors: Voon Kimberly , Simpson Aaron , Fegan Peter Gerard , Walsh John P
Published: July 2023

Non-islet cell tumor hypoglycemia (NICTH) is a rarely encountered cause of hypoglycemia. It is most often caused by tumor secretion of precursor insulin-like growth factor-2 (IGF-2) which, in high concentrations, binds to insulin receptors exerting insulin-like metabolic effects. It is often associated with mesenchymal and hepatic tumors. We describe 3 cases of NICTH: a 60-year-old man with an unresectable pelvic sarcoma and two women ages 43 and 57 with metastatic hemangiopericytoma. Biochemical assessment identified hypoglycemia associated with suppressed insulin, c-peptide, and beta-hydroxybutyrate levels. Each patient was treated with oral glucocorticoids, which effectively prevented recurrence of hypoglycemia and this effect was sustained long-term. These cases highlight a rarely encountered but important cause of hypoglycemia and demonstrate the long-term efficacy of glucocorticoid treatment in preventing hypoglycemia in cases of NICTH related to surgically unresectable tumors.
Mechanomyography as a Surgical Adjunct for Treatment of Chronic Entrapment Neuropathy: A Case Series
Authors: Javeed Saad , Birenbaum Nathan , Xu Yameng , Dibble Christopher F. , Greenberg Jacob K. , Zhang Justin K. , Benedict Braeden , Sydnor Kiersten , Dy Christopher J. , Brogan David M. , Faraji Amir H. , Spinner Robert J. , Ray Wilson Z.
Published: July 2023

BACKGROUND:

Chronic entrapment neuropathy results in a clinical syndrome ranging from mild pain to debilitating atrophy. There remains a lack of objective metrics that quantify nerve dysfunction and guide surgical decision-making. Mechanomyography (MMG) reflects mechanical motor activity after stimulation of neuromuscular tissue and may indicate underlying nerve dysfunction.

OBJECTIVE:

To evaluate the role of MMG as a surgical adjunct in treating chronic entrapment neuropathies.

METHODS:

Patients 18 years or older with cubital tunnel syndrome (n = 8) and common peroneal neuropathy (n = 15) were enrolled. Surgical decompression of entrapped nerves was performed with intraoperative MMG of the hypothenar and tibialis anterior muscles. MMG stimulus thresholds (MMG-st) were correlated with compound muscle action potential (CMAP), motor nerve conduction velocity, baseline functional status, and clinical outcomes.

RESULTS:

After nerve decompression, MMG-st significantly reduced, the mean reduction of 0.5 mA (95% CI: 0.3-0.7, P < .001). On bivariate analysis, MMG-st exhibited significant negative correlation with common peroneal nerve CMAP (P < .05), but no association with ulnar nerve CMAP and motor nerve conduction velocity. On preoperative electrodiagnosis, 60% of nerves had axonal loss and 40% had conduction block. The MMG-st was higher in the nerves with axonal loss as compared with the nerves with conduction block. MMG-st was negatively correlated with preoperative hand strength (grip/pinch) and foot-dorsiflexion/toe-extension strength (P < .05). At the final visit, MMG-st significantly correlated with pain, PROMIS-10 physical function, and Oswestry Disability Index (P < .05).

CONCLUSION:

MMG-st may serve as a surgical adjunct indicating axonal integrity in chronic entrapment neuropathies which may aid in clinical decision-making and prognostication of functional outcomes.
Deletion of taf1 and taf5 in zebrafish capitulate cardiac and craniofacial abnormalities associated with TAFopathies through perturbations in metabolism
Authors: Leid Jamison , Gray Ryan , Rakita Peter , Koenig Andrew L. , Tripathy Rohan , Fitzpatrick James A. J. , Kaufman Charles , Solnica-Krezel Lilianna , Lavine Kory J.
Published: July 2023

Intellectual disability is a neurodevelopmental disorder that affects 2-3% of the general population. Syndromic forms of intellectual disability frequently have a genetic basis and are often accompanied by additional developmental anomalies. Pathogenic variants in components of TATA-binding protein associated factors (TAFs) have recently been identified in a subset of patients with intellectual disability, craniofacial hypoplasia, and congenital heart disease. This syndrome has been termed as a TAFopathy and includes mutations in TATA binding protein (TBP), TAF1, TAF2, and TAF6. The underlying mechanism by which TAFopathies give rise to neurodevelopmental, craniofacial, and cardiac abnormalities remains to be defined. Through a forward genetic screen in zebrafish, we have recovered a recessive mutant phenotype characterized by craniofacial hypoplasia, ventricular hypoplasia, heart failure at 96 h post-fertilization and lethality, and show it is caused by a nonsense mutation in taf5. CRISPR/CAS9 mediated gene editing revealed that these defects where phenocopied by mutations in taf1 and taf5. Mechanistically, taf5-/- zebrafish displayed misregulation in metabolic gene expression and metabolism as evidenced by RNA sequencing, respiration assays, and metabolite studies. Collectively, these findings suggest that the TAF complex may contribute to neurologic, craniofacial, and cardiac development through regulation of metabolism.
Innervation of the developing kidney in vivo and in vitro
Authors: Tarnick Julia , Elhendawi Mona , Holland Ian , Chang Ziyuan , Davies Jamie A.
Published: July 2023

Within the adult kidney, renal neurites can be observed alongside the arteries where they play a role in regulating blood flow. However, their role and localization during development has so far not been described in detail. In other tissues, such as the skin of developing limb buds, neurons play an important role during arterial differentiation. Here, we aim to investigate whether renal nerves could potentially carry out a similar role during arterial development in the mouse kidney. In order to do so, we used whole-mount immunofluorescence staining to identify whether the timing of neuronal innervation correlates with the recruitment of arterial smooth muscle cells. Our results show that neurites innervate the kidney between day 13.5 and 14.5 of development, arriving after the recruitment of smooth muscle actin-positive cells to the renal arteries.