bluuebunny/crossref_metadata_2025 huggingface dataset:
Unlocking the Untapped Hydrocarbon Potenial of the Darduma Member as an Unconventional Reservoir in the Obayied Field, Western Desert, Egypt
Authors: Taha Ahmed , Mostafa Alaa Abu
Published: October 2024

Active exploration efforts are required to replace the produced reserves to guarantee future income and maintain production quotas. This approach can be achieved by exploring new blocks or by drill deeper in old developing blocks to explore new levels (e.g. Paleozoic) or by exploring unconventional reservoirs. The world exploration trends now are towards unconventional reservoirs due to its long production history, but we have few if no mature trials in this trend. The objective of this work is to assess the prospectivity of Darduma limestone because it is thought to offer opportunity to delineate new reserves.

The Obaiyed field (Fig. 1) is one of the largest gas producing fields in the Western Desert. It is located on one of Western Terraces of Matruh Basin. The field is mainly producing from the Jurassic Lower Safa Reservoir in addition to some thin sands within the Upper Safa Member. The Cumulative Production from Gas is 942,310 MMscf. and from Condensate is 57,930,000 bbl.

Darduma Member is the lowermost part of Masajid Formation, which consists mainly of limestone with minor shale streaks. It underlain by Zahra Member of Khatatba Formation (Fig. 2). It is have nearly constant thickness with average thickness of about 100m.
Harsh Environmental Effects on Low Density Fly Ash Proppants
Authors: Haydar Raz , Fakher Sherif
Published: October 2024

Proppants are essential components in hydraulic fracturing for reservoir stimulation, ensuring that fractures maintain conductivity. In high-pressure or harsh environments, high-strength, durable proppants are typically used. However, these proppants are expensive and require costly fracture fluids. This research focuses on developing a new type of proppant that is ultra lightweight, durabile, resistant to corrosion and erosion, and economical. Fly ash, a by-product of various combustion processes, particularly from coal plants, was used to create this new proppant. Fly ash-based proppant formulated is durable, environmentally friendly, buoyant, and cost-effective. To develop the fly ash-based proppant, an alkaline solution was used as an activator and binder. The proppant samples were tested under high temperature and pressure, as well as in acidic, alkaline, saline, and crude oil environments to evaluate their durability. Density was also assessed to determine the buoyancy of the proppant, which affects the fracturing fluid selection. The mix designs included weight ratios of 20%, 22%, and 25% binder, with a fixed 25% water content in all mix designs. After environmental testing, the B20W25 mix design demonstrated satisfactory results across all tests, showing minor erosion and deterioration. Conversely, the B25W25 mix did not withstand the more aggressive environmental conditions and had lower-than-required compressive strength. The density of the three mix designs ranged from 1.33 to 1.35 g/cm3, being categorized as ultra lightweight proppants, making them lighter than sand and thus highly buoyant.
An Innovative Approach to Perform Cement Packer in a Well with Multiple Leak Issues
Authors: Choo D. J. , Farazell S. I.
Published: October 2024

Reserves was realized above top packer and a barrier was needed to segregate the new producing zone from the gas lift. Cement packer job was called forth to spot cement in tubing-casing annulus (casing). A conventional cement packer job will punch a hole in the tubing above a set plug. This allows circulation from tubing into casing to spot cement in the casing. For the job to be successful, the tubing integrity, casing integrity and top packer integrity must be intact for proper placement of cement in the casing. However, a well's completion integrity was found to be compromised. This well has multiple leaks in the completion rendered the conventional cement packer methodology ineffective. The complexity of the challenges had led to compare the options of performing cement packer using coiled tubing (CT) against performing well workover. A new cement packer methodology was devised to tackle the leaks in short string, leaks in long string and leaks at top packer. Sealant was used to reduce the leak at top packer. Retrievable bridge plug was used to control the leak in long string. Modified cement retainer and CT tension set packer were deployed for a successful cement placement in the casing via short string, bypassing the leaks in short string. New producing zone was perforated through the cement packer and no communication between producing zone to the gas lift area was seen indicating a successful cement placement in the casing that act as packer. This successful method had safe client from doing workover on the well. Plus, this method allows future possibility of performing cement packer with tubing integrity issue, unlocking more potential reserves behind casing to be produced.
Reducing Mud Loss in Drilling Operations with High-Performance Plugging Agent
Authors: Xiao Fengfeng , Zhu Jun , Ran Qihua , Liu Gang , Jiang Guancheng , Zhao Zhengguo , Zhang Wei , Li Jingzhe
Published: October 2024

This study aims to evaluate the efficacy of a new high filtration loss consolidation plugging agent in addressing the persistent challenges associated with fluid loss. By conducting comprehensive laboratory experiments and field trials, the aim is to precisely quantify the agent's ability to mitigate fluid loss and enhance wellbore stability. The overarching goal is to provide actionable insights that empower drilling engineers and operators to make informed decisions, leading to improved drilling performance and cost-effectiveness. A methodical approach was employed to assess the high filtration loss consolidation plugging agent's performance. Laboratory experiments simulated downhole conditions by varying temperature, pressure, and salinity, while field trials across diverse drilling sites validated its effectiveness. The agent was applied alongside oil-based drilling fluids, with continuous monitoring of wellbore stability and fluid properties. Advanced analytical techniques, including fluid loss measurements and core sample evaluations, quantified its efficacy. Data analysis guided the optimization of drilling practices. The plugging agent's versatility was demonstrated through its ability to adjust slurry density within the range of 1.0 g/cm3 to 2.2 g/cm3, ensuring applicability across diverse density segments encountered in field operations. With a filtration time of under 60 seconds and a robust consolidation strength exceeding 4 MPa, the agent swiftly forms a solid plugging wall within the leakage channel, effectively enhancing plugging efficiency. In conclusion, field trials were successfully conducted in 25 wells, exemplified by the MX019-H5 well, showcased a remarkable 91.9% reduction in leakage rates, while the WBQ020-H1 well successfully achieved pressure plugging without leakage during circulation at 35 L/s, validating its operational effectiveness. By leveraging the unique properties of the high filtration loss consolidation plugging agent, significant advancements have been made in mitigating fluid loss and improving wellbore stability. The economic implications of these improvements are substantial, with potential cost savings attributed to reduced non-productive time and enhanced drilling performance.
Tailored Solution for Mitigating PDC Bit Balling Challenges in Drilling Sticky Shale
Authors: Feroze Nouman , Case Matt , Al lawati Yousuf , Al Wardi Yasser , ALRawahi Mohammed , Parasher Mukesh
Published: October 2024

Drilling in sticky shale formations presents a tough challenge due to bit balling, where traditional solutions such as oil-based mud not only strain finances but also harm the environment. Conversely, while water-based mud offers a more economical alternative, it increases the risk of bit balling, resulting in frequent bit trips and reduced rates of penetration (ROP), thereby escalating overall well costs.

To combat the risk of bit balling in water-based mud, the focus must be directed towards three pivotal factors: 1. suitable drilling mud composition, 2. appropriate drill bit design, and 3. proper drilling parameters. Neglecting any of these elements can lead to decreased ROP and increased bit trips.

This paper will focus on the design features of PDC drill bits tailored specifically to address PDC bit-balling challenges, such as effectively evacuating cuttings from the cutter's face out of the junk slots and providing sufficient space on the bit face to avoid creating formation cuttings lumps. Two key features crucial for addressing these challenges in PDC drill bits are: 1. optimizing bit face volume and 2. hydraulic enhancement through computational fluid dynamics (CFD).

A pioneering approach utilizing CFD optimization has been devised to customize fluid distribution based on the displacement of the formation by each cutter. This innovative technique ensures that cutters exerting greater work on the formation receive proportionately higher fluid volumes, effectively mitigating bit balling. Additionally, the study examines the optimization of PDC bit face volume without compromising diamond volume.

Test conducted on a bit design employing these methodologies yielded promising results, affirming their ability to overcome bit-balling challenges.
Retrofitting Conventional Wells With Sub-Surface Safety Valve Without a Rig
Authors: Ubedulla Shaik Saheb , Maclurg Michael , Negi R. S , Menon A. , Bota D.
Published: October 2024

It is widely accepted that the absence of safety valves in the completion tubing compromises operational integrity, exposing

operators to potentially severe consequences. This underscores the need for robust safety measures. In the past, a workover was the only way to tackle this problem. The technique we have developed effectively addresses this challenge. Coupled with a penetration point at the wellhead, this system employs a retrievable packer with a safety valve giving the flexibility for the Safety Valve to be retrofitted at any depth within the tubing.

The implementation of this system necessitates the modification of the wellhead to accommodate an inlet for the control line. The safety valve is hung directly off the bottom of the retrievable packer. A stinger is then inserted into the receiving profile in the system at the same time as the control line hanger is located into the penetration profile in the wellhead. Hydraulic communication is thereby created from the safety valve hung below to the control line hanger landed in the wellhead.

The control line transmits safety valve control line pressure through the control line hanger, down to the stinger, and finally into the safety valve ensuring proper valve operation. With the help of this system old wells can be brought back into production without the need of costly workovers and with minimal footprint.

With the pressure on oil and gas industry to move towards sustainable development and reduce carbon emissions, this system presents an innovative approach to installing safety valves into a well without rig intervention, thereby contributing to carbon emission reduction. This system can not only be used on wells with no safety valves but can also be used when the nipple profile, the seal bore, or the flow tube has been damaged or if there is a leak in the previously installed control line.
Pioneering Sustainable Well Cementing in Brunei: Reduced Portland Cement Blends With Locally Sourced Fly Ash
Authors: Suri Chitra Charan , Yeo Chun Kiat , Hugentobler Kory , Simmadorai Dinesh
Published: October 2024

The oil and gas industry in Brunei is increasingly focused on sustainable practices, particularly in well cementing, which is a crucial operation with environmental considerations. To contribute to this effort, the service company has introduced a novel reduced Portland cement (RPC) blend system. This system incorporates locally sourced fly ash, which provides a high-performance and environmentally responsible solution that aligns with the commitment to sustainable development. The RPC system prioritizes environmental stewardship with a decrease in carbon dioxide (CO2) emissions associated with clinker production through a 25% reduction in Class G Portland cement content. Additionally, the system uses readily available fly ash, a recycled material, to minimize reliance on imported ordinary Portland cement (OPC) and strengthen supply chain efficiency.

This focus on localization not only reduces transportation emissions but also fosters a more adaptable and resilient supply network in Brunei. Rigorous laboratory tests have qualified the RPC blend system and have demonstrated that RPC blends maintain or even exceed the compressive strength of conventional, higher-density OPC systems. This helps ensure effective wellbore isolation, despite the lower density of the RPC blend, a crucial factor for long-term well integrity. Additionally, RPC blends exhibit lower equivalent circulating densities, which makes pressure management during wellbore construction simpler and enhances operational efficiency.

The RPC system provides several advantages beyond its environmental benefits. The enhanced ductility and toughness of these blends, compared to traditional cement, allow the cement sheath to better withstand downhole stresses and strain throughout the well's life. This promotes long-term zonal isolation and helps mitigate the potential risk of leakage. Furthermore, the lower permeability of RPC blends provides superior resistance to corrosive fluid and gas that migrate through the wellbore to help ensure the long-term integrity and production efficiency of the well.

Since May 2023, the RPC blend system has been successfully implemented in Brunei. This innovative approach not only minimizes the environmental impact but also delivers strong wellbore integrity. The RPC blend system represents a significant advancement in sustainable well cement operations, which paves the way for a more environmentally acceptable future for the oil and gas industry in Brunei.
Addressing Operational Complexities: Successful Zonal Isolation in Deep Production Liners Through Innovative Cementing
Authors: Quintero E. , Gomez G. , Martanto R. , Edgar D. , Masoud R. , Pohl J. , Iturrios C.
Published: October 2024

This paper explores the complexities involved in achieving zonal isolation within deep production liners with a narrow operational window (pore-fracture pressure). It examines the technical hurdles encountered in this process and presents two comprehensive case histories that illustrates the successful application of innovative cementing techniques. By showcasing these advanced methods, the paper highlights effective strategies for overcoming the inherent challenges of zonal isolation, thereby enhancing the integrity and performance of deep production liners.

The approach involved utilizing an expandable liner hanger system, managed pressure cementing (MPC), environmentally conscious lost circulation spacer, and an engineered cement slurry. Thorough consideration of fluid properties and multiple placement simulations enhanced the accuracy of cement placement. The cases examined a 7-inch and 4½-inch liner, where the deviated sections were drilled from a preceding 9⅝-inch casing string to a target depth of 13,300 feet using a managed pressure drilling (MPD) technique for both cases. An expandable liner top packer was deployed, and contingency measures were implemented to mitigate risks associated with top packer failure.

The application of these innovative cementing techniques achieved successful zonal isolation despite the challenging well conditions. The deployment of the expandable liner hanger system and implementation of contingency measures effectively addressed operational complexities. Managed pressure cementing and eco-friendly lost circulation spacers contributed to the achievement of zonal isolation. Extensive simulations ensured achieving stability of the well during the cementing operation. The engineering procedures and consideration of potential contingencies were critical in accomplishing the objective. This case study underscores the importance of adaptive design and careful planning in cementing operations, providing valuable insights for enhancing zonal isolation practices in deep production liners within the drilling and cementing industries.

This case study introduces a novel approach to achieving zonal isolation in deep production liners by effectively utilizing advanced cementing techniques. The successful application of expandable liner hanger systems, managed pressure cementing techniques, and environmentally friendly lost circulation spacers provides insights for enhancing cementing practices. Additionally, this study explores the integration of advanced technologies and methods that improve the reliability and efficiency of cementing operations.
Identification of Poor Hydrocarbon Chargeability in Initially Pressured Reservoir Using Initial Water Saturation, Formation Tester Mobility, and Movable Hydrocarbon, Basal Alam El Bueib 3A Reservoir, AEB-3C Field, Western Desert, Egypt
Authors: Orban A. , Vaughan R. D. , Ragab I.
Published: October 2024

The integration of initial water saturation (Swi) with movable hydrocarbon (Smo) can demonstrate the charging capacity of a reservoir under initial pressure regardless of the hydrocarbon fluid gradient.

In an initially pressured reservoir with oil gradient, high initial calculated water saturation, good mobility, and low calculated movable hydrocarbon (Smo), in which the study integrates these reservoir characteristics, the risk of running casing or encountering a well test with 100% water cut can be mitigated.

The AEB-3C field was discovered in August 2010 by El Hamra Oil Company (EHO) with the drilling of AEB-3C-1X well to be the first commercial oil discovery in the field through production testing at about 500 BOPD of 23.3°API from the AEB-3A sands reservoir.

The Basal AEB-3A (B.AEB-3A) reservoir comprises three distinct sand bodies was formed in a depositional setting characterized by lower intertidal-subtidal conditions and distributary mouth sand bars. The environmental setting allows for penetrating various sand bars under initial conditions within the same field.

In Well AEB-3C-6, the third sand body within the B.AEB-3A reservoir exhibits a fluid gradient of 0.39 psi/ft, alongside an average mobility of 30 mD/CP (millidarcies per centipoise). Initial water saturation (Sw) was determined using the Archie Equation and used in establishing a water saturation (Sw) height function to describe the difference in initial water saturation (Swi) by porosity band, assuming a clean sandstone reservoir concluded from Cation Exchange Capacity (CEC). The reservoir yielded an average Sw of 60%. The movable hydrocarbon, however, was interpreted conservatively, consistently remaining below 5% and far from the expected value. The primary challenge involved casing installation and reservoir testing. This paper aims to illustrate the integration between Swi and Smo concerning initial reservoir pressure in comparison to the producing wells, while also addressing associated risks and results.
Cost-Effective Solution to a Tar Pump Perennial Performance Problem
Authors: Abidogun Kamorudeen
Published: October 2024

Two identical gear pumps, designed for a maximum speed of 800 RPM, are each rated for a flow of 2.5 m3/hr, 1.5 break horsepower, 160 RPM speed, and a discharge pressure of 750 kPa a. The electric motor driving the pumps through a gear reducer has an output speed of 1800 RPM. With a gear reducer ratio of 5.6:1, the maximum speed of the gear pump is 320 RPM. The pumps are designed to recycle residual styrene tar back to the process as inhibitor in a Styrene plant. Since commissioning, the pumps discharge pressure is insufficient to return the tar back to the process per design. Instead, it is delivered to low pressure utilities area to be flared. Flaring of the styrene tar, due to insufficient pump head, resulted in the loss of inhibitor and styrene monomer. An estimated sum of $ 0.7 MM is lost per year to procure the required inhibitor due to this problem. The investigation commenced with the review of the gear pump as-built datasheet and characteristic curve. A field sample of the tar was taken for lab analysis to determine, among others, its viscosity and specific gravity. The viscosity of the actual tar in the field is multiple times the viscosity of the tar in the as-built datasheet. Parametric studies were conducted that confirmed that the pump performance is in line with the characteristic curve but limited in the discharge pressure due to the limiting pump speed. An appropriate limiting pump speed was calculated, based on the actual fluid properties in the field, to be 600 RPM. As such, the gear reducer ratio was proposed to be changed to 3:1 from the current ratio of 5.6:1. The proposal was implemented first on the installed spare pump and tested with astounding result – the perennial gear pump problem was resolved. The gear reducer was subsequently changed on the main pump as well. The low pump head problem was resolved with negligible CAPEX, no downtime nor major redesign of the piping system.
Novel Wellbore Strengthening Spacer and Managed Pressure Cementing Facilitates Cement Placement in Deep and Shallow Sections Under Narrow Operating Window and Partial Losses
Authors: Shafqat A. , Al-Jadhar A. , Kharchi S. , Mclellan J. , Pohl J.
Published: October 2024

Drilling hydrocarbon-producing wells frequently involves challenges such as narrow operating windows and lost circulation. This paper details the design, execution, and evaluation of primary cementing operations in two case studies of primary cementing operations for intermediate and production sections. This includes operations with complex conditions such as high-pressure/high-temperature (HPHT) conditions, narrow equivalent circulating density (ECD) operating windows due to narrow annular clearances, high pore pressure, and fragile carbonate formations that have a tendency for lost circulation scenarios.

Managed pressure cementing (MPC) techniques have been implemented to allow faster operational response to formation fluids influx or fluid-loss scenarios, thus controlling drilling fluids in the well below the formation pressure by adding a surface annular pressure through a choke manifold. A novel wellbore strengthening spacer, coupled with an environmentally friendly lost circulation material, was successfully deployed, enabling the placement of cement slurries and ensuring wellbore isolation. In these case studies, the combination of the managed pressure system, wellbore strengthening spacer, and the lost circulation additive proved to be effective in addressing and preventing lost circulation scenarios under challenging conditions.
Reservoir Characterization Using 3d Obn Seismic Survey - Cheleken Asset Case Study
Authors: Khdhaouria Mourad , Rondon Aldrin , Ameish Giamal , Rouis Lamia
Published: October 2024

The Cheleken Area lies in the Turkmenistan sector of the South Caspian Sea, over an area of 920 Km2 and in water depth of 10 to 40 m.

Located in a complex wrench faulted system orientated WNW-ESE from the Apsheron Peninsula in Azerbaijan to the Cheleken Peninsula in Turkmenistan, the cheleken fields have a large thickness of stack sand and shale reservoirs, with significant areal and vertical variation.

The field is covered by legacy 3D OBC seismic data acquired and processed in 2004 and reprocessed in 2017 which served as a guide during the exploration and appraisal wells however it presented a lot of limitations in data quality and resolution.

In 2022, another step change in data quality was achieved with the acquisition of the first ever Ocean Bottom Node seismic survey acquired in Turkmenistan. Using high-resolution seismic parameters leads to much better image quality and overcome the majority of subsurface challenges.

The image quality enhancement over this area of shallow water depth was the results of good seismic survey design and a proper seismic processing workflow based mainly on a good velocity model building.

The targets in the current oilfield are variable in depth and thickness and to end up with a better understanding and delineation of the several reservoirs in the studied area, a seismic inversion, as an important tool used in reservoir characterization, was carried out as well as a pore pressure prediction evaluation using seismic velocity.

By combining well data and seismic data, we were able to predict rock properties away from borehole and get better understanding of the reservoirs extension.

Seismic inversion and attribute techniques could be the solution to predict reservoir quality. During the current reservoir characterization study, we used seismic data, well logs, seismic velocity as well as the interpreted horizons to generate impedance data and describe vertically and laterally the different reservoirs in a proper way and minimize the risk for the future drilling activities.
Dynamic Neural Network Modulation Associated with Rumination in Major Depressive Disorder: A Prospective Observational Comparative Analysis of Cognitive Behavioral Therapy and Pharmacotherapy
Authors: Katayama Nariko , Shinagawa Kazushi , Hirano Jinichi , Kobayashi Yuki , Nakagawa Atsuo , Umeda Satoshi , Kamiya Kei , Tajima Miyuki , Amano Mizuki , Nogami Waka , Ihara Sakae , Noda Sachiko , Terasawa Yuri , Kikuchi Toshiaki , Uchida Hiroyuki , Mimura Masaru
Published: October 2024

Cognitive behavioral therapy (CBT) and pharmacotherapy are primary treatments for major depressive disorder (MDD). However, their effects on the neural networks associated with rumination, or repetitive negative thinking, remain poorly understood. This study included 135 participants, whose rumination severity was measured using the rumination response scale (RRS) and whose resting brain activity was measured using functional magnetic resonance imaging (MRI) at baseline and after 16 weeks. MDD patients received either CBT or pharmacotherapy. Using a hidden Markov model, we observed that MDD patients exhibited increased activity in the default mode network (DMN) and decreased occupancies in the sensorimotor and central executive networks (CEN). The DMN occurrence rate correlated positively with rumination severity. CBT reduced DMN activity and improved transitions to the CEN. Pharmacotherapy shifted DMN activity to the posterior region of the brain. CBT and pharmacotherapy affect brain networks involved in rumination differently in MDD patients, suggesting distinct therapeutic pathways.
Microglial low-affinity FcγR mediates the phagocytic elimination of dopaminergic neurons in Parkinson’s disease degeneration
Authors: Barcia Carlos , Casanova Paola , Saavedra-Lopez Elena , Freitag-Berenguel Irina , Usandizaga Maider , Martínez-Remedios Paula , Gimenez-Montes Claudia , Clinton Elsa , Roig-Martínez Meritxell , Cribaro George
Published: October 2024

Microglia-mediated neuroinflammation contributes to dopaminergic (DA) neurodegeneration in Parkinson’s disease (PD). It is thought that microglial cells interact with DA neurons of the substantia nigra pars compacta (SNpc), the most vulnerable region in parkinsonian neuropathology, playing a critical role through the process of neuronal loss. However, the specific mechanisms by which microglial reactivity is triggered and exerts such a deleterious effect remains unclear. Experimental models of PD in mice have shown that phagocytosis plays an essential role in the elimination of degenerating neurons, suggesting that blocking this microglial function could be beneficial to preserve remaining DA neurons. In the present work, we pinpoint the role of the Fcγ receptor (FcγR) as a potential trigger of microglial phagocytosis in PD. We found that the FcγR is overexpressed in the degenerating SNpc in postmortem samples of PD patients, alongside histological indications of phagocytic microglia. Likewise, experimental models of PD also show increased FcγR expression, together with evidence of similar phagocytosis events. Most importantly, blocking FcγR in vitro, by using neutralizing antibodies, reduced the microglial-mediated elimination of DA cells. High resolution imaging revealed that the FcγR is involved in phagocytic synapse formation, and appeared polarized, and segregated to actin-rich protruding cups, when interacting one-on-one towards single target DA cells. Additionally, by inhibiting FcγR downstream actin-polymerizing signaling Cdc42, microglia were unable to eliminate DA cells. Finally, experiments in vivo, using an experimental model of PD in mouse, revealed that passive immunotherapy with FcγR neutralizing monoclonal antibodies, as well as inhibiting its downstream signaling Cdc42, protect DA neurons from elimination. These results indicate that the FcγR may be a critical factor inducing DA neuron phagocytosis in PD and suggest a novel immunotherapeutic strategy targeting microglia to preserve neuronal loss.
The role of ALK gene and PI3k/Akt/NF - κ B signaling pathway in precancerous lesions of cervical cancer
Authors: Qi Ding , Sun Yiming , Ai Wenxia , Han Buwei , Liang Mingge , Zhang Mingshu , Xia Yonggang , Liu Li
Published: October 2024

The study aimed to unravel the molecular basis of cervical precancerous lesions leveraging bioinformatic tools to pinpoint crucial genes and signaling cascades. A multi-faceted approach was undertaken, commencing with GEO database mining for differential gene expression between CSILs and healthy cervical tissues. STRING 11.0 facilitated protein-protein interaction (PPI) analysis, generating a network visualized in Cytoscape 3.7.2. Gene Ontology (GO) and KEGG pathway enrichment via DAVID illuminated biological functions and pathways associated with identified differentially expressed genes (DEGs). GSEA further refined key genes and enriched modules. Concurrently, qRT-PCR validation on cervical biopsy samples from eligible patients corroborated bioinformatic findings. The analysis pinpointed 371 common DEGs across datasets, leading to the discovery of 102 biological processes, 33 cellular components, 15 molecular functions, 29 significant pathways, and 3 pivotal genes. Clinical assessment linked lesion severity to age, vaginal microbiota characteristics, and ALK gene/PI3K/AKT/NF-κB pathway activity. qRT-PCR verified heightened ALK and PI3K/AKT/NF-κB signaling in high-grade lesions, underscoring their roles in CSIL pathogenesis. The importance of this research lies in its potential to inform the development of targeted therapies and personalized treatment strategies for cervical precancerous lesions. By identifying the molecular drivers of the disease, researchers can design interventions that precisely target these pathways, improving patient outcomes and reducing the burden of cervical cancer.
M6A and lactylation modification-related signature predicts prognosis and immunotherapy response in hepatocellular carcinoma
Authors: Ren Huili , Liu Jianhua , Zhang Shaohui
Published: October 2024

This study aims to investigate the role of lactylation and m6A modification-related genes in the tumor microenvironment and immunotherapy for hepatocellular carcinoma (HCC) patients. RNA-sequence data and corresponding clinical information of HCC were obtained from the TCGA and ICGC datasets. LASSO Cox regression analysis was implied to construct a lactylation-m6A related prognostic model. The 7-gene signature was established and effectively stratified patients into high- and low-risk groups. Further analysis revealed significant differences between the two risk groups in terms of tumor microenvironment, expression levels of immune checkpoint genes, and drug responsiveness. Specifically, the high-risk group exhibited increased immune cell infiltration, lower IC50 values for several drugs including 5-fluorouracil, afatinib, crizotinib, cediranib, taselisib, and staurosporine; Whereas the low-risk group displayed reduced stromal component proportions and better responses to entinostat, irinotecan, KRAS inhibitors, cisplatin, axitinib, and topotecan. Functionally, knockdown of TCOF1 and HDAC1 significantly attenuated the migration and invasive capacity of Huh-7 liver cancer cells. The lactylation-m6A related prognostic model exhibited robust predictive efficiency in HCC. TCOF1 and HDAC1 may be promising tumor biomarkers for HCC and more researches are needed to validate these results.
An exploration of the correlation between strain energy density in the temporomandibular joint and facial morphologic parameters
Authors: Murakami Kazuhiro , Kawakami Masayoshi , Yamamoto Kazuhiko , Horita Satoshi
Published: October 2024

Purpose: The purpose of this was to construct finite element (FE) models based on computed tomography (CT) data of individual patients during orthodontic treatment and to evaluate the relationship between strain energy density (SED) in the temporomandibular joint (TMJ) disc and the facial morphology of three skeletal patterns (Class 1–3) by cephalometric analysis.
Methods: Cephalometric analyses were performed on 53 patients. FE models based on the CT images of each patient were constructed, and the mean SED in the bilateral TMJ disc was calculated. The relationships between SED and the cephalometric parameters were evaluated.
Results: SED was significantly greater in Classes 1 and 2 than in Class 3 (p < 0.05). A positive correlation was observed between SED and the parameter of, convexity and ANB angle (p < 0.01), whereas a negative correlation was observed between SED and facial angle in Class 3(p < 0.05). A positive correlation was identified between SED and gonial angle in Class 1(p < 0.05). In all cases, correlations were observed between SED and facial angle (p < 0.05), convexity(p < 0.01), mandibular angle(p < 0.05), Y-axis(p < 0.05), SNB (p < 0.05), ANB angle(p < 0.01), and overjet(p < 0.05).
Conclusion: An increase in SED in the TMJ disc was observed when the mandible was rotated clockwise and positioned superior posteriorly. Furthermore, SED was affected by an overjet of dental parameters. Numerically, the present study suggests that SED generated in the TMJ disc was primarily affected by mandibular morphology. Considering that an increase in SED causes damage to the articular disc, three skeletal parameters (facial angle, convexity, and ANB) are useful in predicting TMJ dysfunction.
The Role of Dietary Vitamin E in Preventing Degenerative Musculoskeletal Diseases: Insights from Mendelian Randomization
Authors: jiewen Wei
Published: October 2024

Background
Degenerative musculoskeletal diseases, including osteoarthritis, osteoporosis, intervertebral disc degeneration, and sarcopenia, significantly impair patient mobility and quality of life, particularly in the elderly. Despite extensive research, the pathogenesis of these diseases remains incompletely understood, and effective treatments are lacking. Recent evidence suggests that oxidative stress and inflammation play crucial roles in the development of these conditions. Vitamin E, a potent antioxidant, has been proposed as a potential protective factor.
Objective
To investigate the causal relationship between dietary vitamin E intake and the risk of degenerative musculoskeletal diseases using a two-sample Mendelian randomization (MR) approach.
Methods
I utilized data from the UK Biobank's IEU OpenGWAS, the Finnish FinnGen Biobank, and the PhenoScanner database. Genetic variants associated with vitamin E intake were used as instrumental variables. Outcome data for OA, OP, SP, and IVDD were obtained from large-scale genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was the primary analysis, supported by MR-Egger, weighted median, and other sensitivity analyses to ensure robustness.
Results
The IVW method revealed no significant causal association between vitamin E intake and the risk of OA, OP, SP, or IVDD. Sensitivity analyses, including Cochran’s Q test and the MR-Egger intercept test, indicated no evidence of heterogeneity or horizontal pleiotropy. Leave-one-out analyses confirmed that no single SNP significantly influenced the overall causal effect estimates.
Conclusion
This MR study found no evidence to support a causal relationship between dietary vitamin E intake and the risk of degenerative musculoskeletal diseases. These findings suggest that vitamin E supplementation may not be effective in preventing or managing these conditions. Future research should explore other potential factors and consider different populations to further understand the role of vitamin E in musculoskeletal health.
Utility of simplified echocardiographic criteria for diagnosing subclinical rheumatic heart disease among primary and secondary school scholars in Kondoa District, Dodoma, Tanzania: A cross-sectional study
Authors: Macha Edgar , Baraka Alphonce , Karoli Peter , Kagaruki Gibson , Mayige Mary , Mutagaywa Reuben , Meda John
Published: October 2024

Background: Rheumatic heart disease is among the major causesof morbidity and mortality among children and young adults in low-income countries. Early detection of subclinical rheumatic heart disease and initiation of secondary prophylaxis prevents progression into clinical rheumatic heart disease. In 2012, the World Heart Federation established criteria for the diagnosis of subclinical rheumatic heart disease. However, the applicability and feasibility of screening in low-income settings with insufficient resources has been a setback. The aimof thisstudy was to validate simplified echocardiographic criteria for the diagnosis ofsubclinical rheumatic heart disease.
Methods: A school-based cross-sectional study was conducted among primary and secondary school scholars between the ages of 5 and 20 years in Kondoa District. Eligible primary and secondary school scholars underwent two echocardiographic screens on the basis of simplified echocardiographic criteria by non-expert personnel and then the World Heart Federation criteria of 2012 by expert personnel. Continuous variables are presented as the means with standard deviations or medians with IQRs. Categorical variables are presented as frequencies and percentages. Echocardiographic findings by simplified criteria were compared to the findings of the World Heart Federation 2012. Using cross tabulation in STATA, the utility of the simplified criteria was determined. The two criteria were assessed and compared via the area under the receiver operating characteristic curve (AUC) with a 95% CI.
Results: Of the 2175 participants sampled, only 1618 underwent echocardiographic screening. The prevalence of subclinical RHD was 14 per 1000. Among the 22 children with subclinical rheumatic heart disease, 14 had definite disease, whereas 8 had borderline rheumatic heart disease. The sensitivity, specificity, positive predictive value and negative predictive value of the simplified criteria for the diagnosis of SHCD were 100% (95% CI 100–100%), 99.69% (95% CI 99.41–99.96%), 81.48% (95% CI 79.59–83.37%), and 100% (95% CI 100–100%), respectively. The area under the curve (AUC) for the simplified criteria for diagnosing subclinical RHD was 0.998 (95% CI 0.997–1.000, p < 0.001).
Conclusion: In resource-limited endemic areas with a lack of expert personnel, simplified echocardiographic criteria are useful screening tools for the diagnosis of subclinical Rheumatic Heart Disease.
Transvaginal Repair of Apical Vesicovaginal Fistula via Vaginal Natural Orifice Transluminal Endoscopic Surgery (V-NOTES): A Modified Surgical Technique and Its Outcomes
Authors: Song Xin , Jiang Chen , Lv Jian-wei
Published: October 2024

Objective
To report the procedure of an alternative modified transvaginal repair technique (V-NOTES) and their outcomes in apical vesicovaginal fistula.
Methods
Between January 2020 and January 2023, gynecological procedures resulted in the diagnosis of apical VVFs in 26 patients, 17 of whom had undergone transvaginal repair of apical vesicovaginal fistula via vaginal V-NOTES. Those patients were contacted and followed up. Outcomes included operative time, blood loss, success rate, postoperative hospital stay.
Results
The average age of the patients was 45.82(36–53) yr. The mean duration between onset of fistula and repair was 7.18(3–12) mo. The mean estimated blood loss was 10.45 ± 3.23ml, and the average operative time was 104.2 ± 12.2min. Patients’ postoperative hospital stay was 3.34 ± 0.72 days on average. The VVF was successfully repaired in 15(88.2%) cases, and failure was observed in 2 patients. All the 2 initial failures were cured in the second repair. No major complications developed in all 17 patients. There were also no fever (> 38℃), urge incontinence or infection in incision area.
Conclusions
Our study suggest that the transvaginal repair of apical VVF via V-NOTES is effective and safety, and offers anticipated results without obvious complications.
Repetitive transcranial magnetic stimulatation alleviates motor impairment in Parkinson's disease: association with peripheral inflammatory regulatory T-cells and SYT6
Authors: Xie Fen , Shen BIbiao , Luo Yuqi , Zhou Hang , Xie Zhenchao , Zhu Shuzhen , Wei Xiaobo , Chang Zihan , Zhu Zhaohua , Ding Changhai , Jin Kunlin , Yang Chengwu , Batzu Lucia , Chaudhuri K Ray , Chan Ling-Ling , Tan Eng-King , Wang Qing
Published: October 2024

Background
Repetitive transcranial magnetic stimulation (rTMS) has been used to treat various neurological disorders. However, the molecular mechanism underlying the therapeutic effect of rTMS on Parkinson’s disease (PD) has not been fully elucidated. Neuroinflammation like regulatory T-cells (Tregs) appears to be a key modulator of disease progression in PD. If rTMS affects the peripheral Tregs in PD remains unknown.
Methods
Here, we conducted a prospective clinical study (Chinese ClinicalTrials. gov: ChiCTR 2100051140) involving 54 PD patients who received 10-day rTMS (10 Hz) stimulation on the primary motor cortex (M1) region or sham treatment. Clinical and function assessment as well as flow cytology study were undertaken in 54 PD patients who were consecutively recruited from the department of neurology at Zhujiang hospital between September 2021 and January 2022. Subsequently, we implemented flow cytometry analysis to examine the Tregs population in spleen of MPTP-induced PD mice that received rTMS or sham treatment, along with quantitative proteomic approach reveal novel molecular targets for Parkinson's disease, and finally, the RNA interference method verifies the role of these new molecular targets in the treatment of PD.
Results
We demonstrated that a 10-day rTMS treatment on the M1 motor cortex significantly improved motor dysfunction in PD patients. The beneficial effects persisted for up to 40 days, and were associated with an increase in peripheral Tregs. There was a positive correlation between Tregs and motor improvements in PD cases. Similarly, a 10-day rTMS treatment on the brains of MPTP-induced PD mice significantly ameliorated motor symptoms. rTMS reversed the downregulation of circulating Tregs and tyrosine hydroxylase neurons in these mice. It also increased anti-inflammatory mediators, deactivated microglia, and decreased inflammatory cytokines. These effects were blocked by administration of a Treg inhibitor anti-CD25 antibody in MPTP-induced PD mice. Quantitative proteomic analysis identified TLR4, TH, Slc6a3 and especially Syt6 as the hub node proteins related to Tregs and rTMS therapy. Lastly, we validated the role of Treg and rTMS-related protein syt6 in MPTP mice using the virus interference method.
Conclusions
Our clinical and experimental studies suggest that rTMS improves motor function by modulating the function of Tregs and suppressing toxic neuroinflammation. Hub node proteins (especially Syt6) may be potential therapeutic targets.
Trial registration: Chinese ClinicalTrials, ChiCTR2100051140. Registered 15 December 2021, https://www.chictr.org.cn/bin/project/edit?pid=133691
The Role of Immune Cells in Colorectal Cancer: A Mendelian Randomization Study and Validation in A Single-Center Case-Control Trial.
Authors: Sun Luan-Biao , Zhou XuanPeng , Song Xin-Yuan , Xing Jian-Peng , Gao Shuo-Hui
Published: October 2024

Background: Although a growing body of research suggests that alterations in the composition of the immune system play a critical role in the development of colorectal cancer (CRC), the causal and prognostic relationship between specific immune cells and the risk of CRC development remains unclear.
Method: In this study, Mendelian randomization (MR) was employed to investigate the causal relationship between immunophenotypes and colorectal cancer. To explore the potential associations, five MR methods were applied: Inverse Variance Weighting (IVW), MR-Egger, Weighted Median, Weighted Mode, and Simple mode. If the results of the five methods are inconclusive, we favored the IVW as the primary outcome. In addition, heterogeneity and pleiotropy were tested using MR-Egger, MR-PRESSO-Global, and Cochrane's Q. Stability of MR findings was assessed using leave-one-out approach, and the strength of the causal relationship between exposure and outcome was tested using the Bonferroni correction. Additional single-center clinical case-control samples were utilized to validate the results of Mendelian randomization, and prognostic results were visualized by logistic regression models, COX regression models, and Kaplan-Meier survival curves.
Result: Among 731 immunophenotypes were tested, 26 immunophenotypes were associated with CRC risk. The Bonferroni-corrected testing reveals that Lymphocyte %leukocyte and CD3 on CM CD8br had a significant causal association with CRC. According to Cochrane's Q test, there was no significant heterogeneity across different single-nucleotide polymorphisms. Furthermore, the MR-Egger and MR-PRESSO-Global tests did not show pleiotropy. There was no reverse causality between the CRC risk and immunophenotypes. In the single-center clinical case-control study demonstrated a positive causal relationship between the relative counts of lymphocytes and CD4+T cells and the risk of CRC development. Furthermore, our correlation analysis also demonstrated a potential association between lymphocyte relative counts and poor prognosis in CRC cases.
Conclusion: Through MR analysis, we established a causal relationship between lymphocytes and maturation stages of T cell in the risk of CRC development. Additionally, case-control studies focusing on circulating lymphocytes and their subpopulations have further validated that these cells are integral to both the pathogenesis and prognosis of CRC. This finding may provide valuable ideas for early, noninvasive detection and potential immunotherapeutic targets for CRC.
‘Technology Alone Is Not Enough: The Role of Operational Efficiency in Bridging AI and Patient Outcomes’ – Insights from Taiwanese Healthcare Facilities"
Authors: Hung-Xin Li
Published: October 2024

This research investigates the equitable distribution of healthcare resources and its impact on patient outcomes, along with the relationship between resource allocation strategies and operational efficiency in Taiwan's healthcare system. Using a mixed-methods approach, the study explores these strategies through qualitative data from semi-structured interviews analyzed with NVIVO software and quantitative data collected via surveys from hospital administrators, safety teams, and financial personnel. A sequential random sampling method selected healthcare institutions based on size, location, and specialty services. The findings reveal a strong correlation between the adoption of AI techniques, healthcare quality, patient care service utilization, and improved patient outcomes, although resource allocation alone does not directly affect patient outcomes. Operational efficiency plays a mediating role, contributing to better patient results. The study emphasizes the need for integrating efficient resource management and operational practices to enhance patient outcomes, providing actionable insights for healthcare administrators to improve care quality and accessibility. It also highlights the importance of developing tailored resource management strategies that consider regional and organizational differences within Taiwan’s healthcare system.