Clinical application of whole-genome sequencing of solid tumors for precision oncology.

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management.

Highly Efficient Wide Bandgap Perovskite Solar Cells With Tunneling Junction by Self-Assembled 2D Dielectric Layer.

Reducing non-radiative recombination and addressing band alignment mismatches at interfaces remain major challenges in achieving high-performance wide-bandgap perovskite solar cells. This study proposes the self-organization of a thin two-dimensional (2D) perovskite BA2PbBr4 layer beneath a wide-bandgap three-dimensional (3D) perovskite Cs0.17FA0.83Pb(I0.6Br0.4)3, forming a 2D/3D bilayer structure on a tin oxide (SnO2) layer. This process is driven by interactions between the oxygen vacancies on the SnO2 surface and hydrogen atoms of the n-butylammonium cation, aiding the self-assembly of the BA2PbBr4 2D layer. The 2D perovskite acts as a tunneling layer between SnO2 and the 3D perovskite, neutralizing the energy level mismatch and reducing non-radiative recombination. This results in high power conversion efficiencies of 21.54% and 19.16% for wide-bandgap perovskite solar cells with bandgaps of 1.7 and 1.8 eV, with open-circuit voltages over 1.3 V under 1-Sun illumination. Furthermore, an impressive efficiency of over 43% is achieved under indoor conditions, specifically under 200 lux white light-emitting diode light, yielding an output voltage exceeding 1 V. The device also demonstrates enhanced stability, lasting up to 1,200 hours.

Scanning Probe Microscopy of Halide Perovskite Solar Cells.

Scanning probe microscopy (SPM) has enabled significant new insights into the nanoscale and microscale properties of solar cell materials and underlying working principles of photovoltaic and optoelectronic technology. Various SPM modes, including atomic force microscopy, Kelvin probe force microscopy, conductive atomic force microscopy, piezoresponse force microscopy, and scanning near-field optical microscopy, can be used for the investigation of electrical, optical and chemical properties of associated functional materials. A large body of work has improved the understanding of solar cell device processing and synthesis in close synergy with SPM investigations in recent years. This review provides an overview of SPM measurement capabilities and attainable insight with a focus on recently widely investigated halide perovskite materials.

Fostering Charge Carrier Transport and Absorber Growth Properties in CZTSSe Thin Films with an ALD-SnO2 Capping Layer.

The present study demonstrates that precursor passivation is an effective approach for improving the crystallization process and controlling the detrimental defect density in high-efficiency Cu2ZnSn(S,Se)4 (CZTSSe) thin films. It is achieved by applying the atomic layer deposition (ALD) of the tin oxide (ALD-SnO2) capping layer onto the precursor (Cu-Zn-Sn) thin films. The ALD-SnO2 capping layer was observed to facilitate the homogeneous growth of crystalline grains and mitigate defects prior to sulfo-selenization in CZTSSe thin films. Particularly, the CuZn and SnZn defects and deep defects associated with Sn were effectively mitigated due to the reduction of Sn2+ and the increase in Sn4+ levels in the kesterite CZTSSe film after introducing ALD-SnO2 on the precursor films. Subsequently, devices integrating the ALD-SnO2 layer exhibited significantly reduced recombination and efficient charge transport at the heterojunction interface and within the bulk CZTSSe absorber bulk properties. Finally, the CZTSSe device showed improved power conversion efficiency (PCE) from 8.46% to 10.1%. The incorporation of ALD-SnO2 revealed reduced defect sites, grain boundaries, and surface roughness, improving the performance. This study offers a systematic examination of the correlation between the incorporation of the ALD-SnO2 layer and the improved PCE of CZTSSe thin film solar cells (TFSCs), in addition to innovative approaches for improving absorber quality and defect control to advance the performance of kesterite CZTSSe devices.

Thermal Disorder-Induced Strain and Carrier Localization Activate Reverse Halide Segregation.

The reversal of halide ions is studied under various conditions. However, the underlying mechanism of heat-induced reversal remains unclear. This work finds that dynamic disorder-induced localization of self-trapped polarons and thermal disorder-induced strain (TDIS) can be co-acting drivers of reverse segregation. Localization of polarons results in an order of magnitude decrease in excess carrier density (polaron population), causing a reduced impact of the light-induced strain (LIS - responsible for segregation) on the perovskite framework. Meanwhile, exposing the lattice to TDIS exceeding the LIS can eliminate the photoexcitation-induced strain gradient, as thermal fluctuations of the lattice can mask the LIS strain. Under continuous 0.1 W cm⁻2 illumination (upon segregation), the strain disorder is estimated to be 0.14%, while at 80 °C under dark conditions, the strain is 0.23%. However, in situ heating of the segregated film to 80 °C under continuous illumination (upon reversal) increases the total strain disorder to 0.25%, where TDIS is likely to have a dominant contribution. Therefore, the contribution of entropy to the system's free energy is likely to dominate, respectively. Various temperature-dependent in situ measurements and simulations further support the results. These findings highlight the importance of strain homogenization for designing stable perovskites under real-world operating conditions.

High-Performance Indoor Perovskite Solar Cells by Self-Suppression of Intrinsic Defects via a Facile Solvent-Engineering Strategy.

Lead halide perovskite solar cells have been emerging as very promising candidates for applications in indoor photovoltaics. To maximize their indoor performance, it is of critical importance to suppress intrinsic defects of the perovskite active layer. Herein, a facile solvent-engineering strategy is developed for effective suppression of both surface and bulk defects in lead halide perovskite indoor solar cells, leading to a high efficiency of 35.99% under the indoor illumination of 1000 lux Cool-white light-emitting diodes. Replacing dimethylformamide (DMF) with N-methyl-2-pyrrolidone (NMP) in the perovskite precursor solvent significantly passivates the intrinsic defects within the thus-prepared perovskite films, prolongs the charge carrier lifetimes and reduces non-radiative charge recombination of the devices. Compared to the DMF, the much higher interaction energy between NMP and formamidinium iodide/lead halide contributes to the markedly improved quality of the perovskite thin films with reduced interfacial halide deficiency and non-radiative charge recombination, which in turn enhances the device performance. This work paves the way for developing efficient indoor perovskite solar cells for the increasing demand for power supplies of Internet-of-Things devices.

Physiological gradient in lumbar spine fat fraction and R2* and its impact on osteoporosis diagnosis.

BACKGROUND: Bone marrow adiposity and R2* have been explored as an imaging biomarker for osteoporosis. Chemical shift-encoded MRI (CSE-MRI) is a method that allows for relatively accurate measurement of adiposity and R2* in bone marrow in a simple manner. Additionally, there are reports of a physiological gradient of fat distribution in the lumbar spine. This physiological gradient of fat distribution can potentially impact the prediction of osteoporosis. Furthermore, the distribution of R2* is not well understood. PURPOSE: This study examined how lumbar spine fat fraction (FF) and R2* change with different levels of the lumbar spine, how they influence osteoporosis prediction, and how they change according to measurement methods. STUDY DESIGN/SETTING: Cross-sectional study using retrospectively collected data. PATIENT SAMPLE: The study included patients who underwent dual-energy X-ray absorptiometry and lumbar spine CSE-MRI within one-month intervals between 2017 and 2022. OUTCOME MEASURES: Reproducibility of FF and R2* based on measurement techniques, changes in FF and R2* according to vertebral level and osteoporosis status, and diagnostic power of osteoporosis based on vertebral level. METHODS: Patients were categorized into the normal bone density, osteopenia, and osteoporosis groups based on bone mineral density. The relationship between groups and spine level before and after BMD adjustment was investigated using generalized estimating equations. Comparisons between the three groups and various measures of reliability were conducted using intraclass correlation coefficient. The diagnostic performance for predicting osteoporosis was evaluated with a receiver operating characteristic curve. RESULTS: Comparing the three groups, FF increased with osteoporosis severity, while R2* decreased (p<.001). The intra/inter-rater agreement for FF and R2* was excellent. A physiological gradient within individuals was observed, where FF increased towards the lower lumbar spine (p=.002). R2* tended to decrease, but it was not statistically significant (p=.218). There was no statistically significant difference in the diagnosis of osteoporosis based on FF or R2* across different lumbar spine levels. CONCLUSIONS: There was an increase in FF and a decrease in R2* from T12 to L5. However, the predictive power of osteoporosis did not significantly differ between each level.

Deviation of Latitude Cut: A Simple Sign to Differentiate Total Hip Arthroplasty from Hemiarthroplasty in Radiography.

This study aims to propose latitude cut deviation for differentiating hip arthroplasty types and evaluate its diagnostic utility in distinguishing total hip arthroplasty (THA) from hemiarthroplasty using radiography. After assessing various cup designs from top manufacturers for THA and hemiarthroplasty, we conducted a retrospective study on 40 patients (20 THA and 20 hemiarthroplasty). Three readers independently evaluated the radiographs, assessing acetabular sparing, cup-bone interface texture, and latitude cut deviation. Diagnostic performance and inter-observer agreement were compared using receiver operating characteristic curves and the Fleiss kappa coefficient. Latitude cut deviation measured on implant designs ranged from 19% to 42% in hemiarthroplasty and from -12% to 9% in THA. The sensitivity, specificity, and accuracy used to distinguish THA from hemiarthroplasty were 60-85%, 55-95%, and 62.5-77.5% for acetabular sparing; 100%, 50-80%, and 75-90% for cup-bone interface texture; and 100%, 90-100%, and 95-100% for latitude cut deviation. Inter-observer agreement for acetabular sparing, cup-bone interface texture, and latitude cut deviation ranged from moderate to excellent (κ = 0.499, 0.772, and 0.900, respectively). The latitude cut deviation exhibited excellent diagnostic performance and inter-reader agreement in distinguishing hemiarthroplasty from THA on radiographs, offering a concise way to identify hip arthroplasty type.

CT and MR for bone mineral density and trabecular bone score assessment in osteoporosis evaluation.

Dual energy X-ray absorptiometry (DXA) is widely used modality for measuring bone mineral density (BMD). DXA is used to measure the quantitative areal BMD of bone, but has the disadvantage of not reflecting the bone architecture. To compensate for this disadvantage, trabecular bone score (TBS), a qualitative parameter of trabecular microarchitecture, is used. Meanwhile, there have been recent attempts to diagnose osteoporosis using the Hounsfield unit (HU) from CT and MR-based proton density fat fraction (PDFF) measurements. In our study, we aimed to find out the correlation between HU/PDFF and BMD/TBS, and whether osteoporosis can be diagnosed through HU/PDFF. Our study revealed that the HU value showed a moderate to good positive correlation with BMD and TBS. PDFF showed a fair negative correlation with BMD and TBS. In diagnosing osteopenia and osteoporosis, the HU value showed good performance, whereas the PDFF showed fair performance. In conclusion, both HU values and PDFF can play a role in predicting BMD and TBS. Both HU values and PDFF can be used to predict osteoporosis; further, CT is expected to show better results.

The diagnostic performance and clinical value of deep learning-based nodule detection system concerning influence of location of pulmonary nodule.

BACKGROUND: The deep learning-based nodule detection (DLD) system improves nodule detection performance of observers on chest radiographs (CXRs). However, its performance in different pulmonary nodule (PN) locations remains unknown. METHODS: We divided the CXR intrathoracic region into non-danger zone (NDZ) and danger zone (DZ). The DZ included the lung apices, paramediastinal areas, and retrodiaphragmatic areas, where nodules could be missed. We used a dataset of 300 CXRs (100 normal and 200 abnormal images with 216 PNs [107 NDZ and 109 DZ nodules]). Eight observers (two thoracic radiologists [TRs], two non-thoracic radiologists [NTRs], and four radiology residents [RRs]) interpreted each radiograph with and without the DLD system. The metric of lesion localization fraction (LLF; the number of correctly localized lesions divided by the total number of true lesions) was used to evaluate the diagnostic performance according to the nodule location. RESULTS: The DLD system demonstrated a lower LLF for the detection of DZ nodules (64.2) than that of NDZ nodules (83.2, p = 0.008). For DZ nodule detection, the LLF of the DLD system (64.2) was lower than that of TRs (81.7, p < 0.001), which was comparable to that of NTRs (56.4, p = 0.531) and RRs (56.7, p = 0.459). Nonetheless, the LLF of RRs significantly improved from 56.7 to 65.6 using the DLD system (p = 0.021) for DZ nodule detection. CONCLUSION: The performance of the DLD system was lower in the detection of DZ nodules compared to that of NDZ nodules. Nonetheless, RR performance in detecting DZ nodules improved upon using the DLD system. CRITICAL RELEVANCE STATEMENT: Despite the deep learning-based nodule detection system's limitations in detecting danger zone nodules, it proves beneficial for less-experienced observers by providing valuable assistance in identifying these nodules, thereby advancing nodule detection in clinical practice. KEY POINTS: • The deep learning-based nodule detection (DLD) system can improve the diagnostic performance of observers in nodule detection. • The DLD system shows poor diagnostic performance in detecting danger zone nodules. • For less-experienced observers, the DLD system is helpful in detecting danger zone nodules.

Stabilization of photoactive phases for perovskite photovoltaics.

Interest in photovoltaics (PVs) based on Earth-abundant halide perovskites has increased markedly in recent years owing to the remarkable properties of these materials and their suitability for energy-efficient and scalable solution processing. Formamidinium lead triiodide (FAPbI3)-rich perovskite absorbers have emerged as the frontrunners for commercialization, but commercial success is reliant on the stability meeting the highest industrial standards and the photoactive FAPbI3 phase suffers from instabilities that lead to degradation - an effect that is accelerated under working conditions. Here, we critically assess the current understanding of these phase instabilities and summarize the approaches for stabilizing the desired phases, covering aspects from fundamental research to device engineering. We subsequently analyse the remaining challenges for state-of-the-art perovskite PVs and demonstrate the opportunities to enhance phase stability with ongoing materials discovery and in operando analysis. Finally, we propose future directions towards upscaling perovskite modules, multijunction PVs and other potential applications.

Adjusted Bulk and Interfacial Properties in Highly Stable Semitransparent Perovskite Solar Cells Fabricated by Thermocompression Bonding between Perovskite Layers.

In order to shield perovskite solar cells (PSCs) from extrinsic degradation factors and ensure long-term stability, effective encapsulation technology is indispensable. Here, a facile process is developed to create a glass-glass encapsulated semitransparent PSC using thermocompression bonding. From quantifying the interfacial adhesion energy and considering the power conversion efficiency of devices, it is confirmed that bonding between perovskite layers formed on a hole transport layer (HTL)/indium-doped tin oxide (ITO) glass and an electron transport layer (ETL)/ITO glass can offer an excellent lamination method. The PSCs fabricated through this process have only buried interfaces between the perovskite layer and both charge transport layers as the perovskite surface is transformed into bulk. The thermocompression process leads the perovskite to have larger grains and smoother, denser interfaces, thereby not only reducing defect and trap density but also suppressing ion migration and phase segregation under illumination. In addition, the laminated perovskite demonstrates enhanced stability against water. The self-encapsulated semitransparent PSCs with a wide-band-gap perovskite (Eg ∼ 1.67 eV) demonstrate a power conversion efficiency of 17.24% and maintain long-term stability with PCE > ∼90% in the 85 °C shelf test for over 3000 h and with PCE > ∼95% under AM 1.5 G, 1-sun illumination in an ambient atmosphere for over 600 h.

[Correlation Analysis between Fat Fraction and Bone Mineral Density Using the DIXON Method for Fat Dominant Tissue in Knee Joint MRI: A Preliminary Study]. / 지방우세 딕슨기법을 이용한 ìŠ¬ê´€ì ˆ ìžê¸°ê³µëª ì˜ìƒ ì§€ë°©ì‹ í˜¸ë¶„ìœ¨ê³¼ 골밀도 간의 상관관계 분석: 예비 연구.

Purpose: This study aimed to investigate the correlation between the fat signal fraction (FF) of the fat-dominant bone tissue of the knee joint, measured using the MRI Dixon method (DIXON) technique, and bone mineral density (BMD). Materials and Methods: Among the patients who underwent knee DIXON imaging at our institute, we retrospectively analyzed 93 patients who also underwent dual energy X-ray absorptiometry within 1 year. The FFs of the distal femur metaphyseal (Fm) and proximal tibia metaphyseal (Tm) were calculated from the DIXON images, and the correlation between FF and BMD was analyzed. Patients were grouped based on BMD of lumbar spine (L), femoral neck (FN), and common femur (FT) respectively, and the Kruskal-Wallis H test was performed for FF. Results: We identified a significant negative correlation between TmFF and FN-BMD in the entire patient group (r = -0.26, p < 0.05). In female patients, TmFF showed a negative correlation with FN-BMD, FT-BMD, and L-BMD (r = -0.38, 0.28 and -0.27, p < 0.05). In male patients, FmFF was negatively correlated with only FN-BMD and FT-BMD (r = -0.58 and -0.42, p < 0.05). There was a significant difference in the TmFF between female patients grouped by BMD (p < 0.05). In male patients, there was a significant difference in FmFF (p < 0.05). Conclusion: Overall, we found that FF and BMD around the knee joints showed a negative correlation. This suggests the potential of FF measurement using DIXON for BMD screening.

Suppressing Halide Segregation in Wide-Band-Gap Mixed-Halide Perovskite Layers through Post-Hot Pressing.

Mixed-halide perovskites (MHPs) have attracted attention as suitable wide-band-gap candidate materials for tandem applications owing to their facile band-gap tuning. However, when smaller bromide ions are incorporated into iodides to tune the band gap, photoinduced halide segregation occurs, which leads to voltage deficit and photoinstability. Here, we propose an original post-hot pressing (PHP) treatment that suppresses halide segregation in MHPs with a band gap of 2.0 eV. The PHP treatment reconstructs open-structured grain boundaries (GBs) as compact GBs through constrained grain growth in the in-plane direction, resulting in the inhibition of defect-mediated ion migration in GBs. The PHP-treated wide-band-gap (2.0 eV) MHP solar cells showed a high efficiency of over 11%, achieving an open-circuit voltage (Voc) of 1.35 V and improving the maintenance of the initial efficiency under the working condition at AM 1.5G. The results reveal that the management of GBs is necessary to secure the stability of wide-band-gap MHP devices in terms of halide segregation.

Revealing the Dynamics of the Thermal Reaction between Copper and Mixed Halide Perovskite Solar Cells.

Copper (Cu) is present not only in the electrode for inverted-structure halide perovskite solar cells (PSCs) but also in transport layers such as copper iodide (CuI), copper thiocyanate (CuSCN), and copper phthalocyanine (CuPc) alternatives to spiro-OMeTAD due to their improved thermal stability. While Cu or Cu-incorporated materials have been effectively utilized in halide perovskites, there is a lack of thorough investigation on the direct reaction between Cu and a perovskite under thermal stress. In this study, we investigated the thermal reaction between Cu and a perovskite as well as the degradation mechanism by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Kelvin probe force microscopy (KPFM). The results show that high temperatures of 100 °C induce Cu to be incorporated into the perovskite lattice by forming "Cu-rich yet organic A-site-poor" perovskites, (CuxA1-x)PbX3, near the grain boundaries, which result in device performance degradation.

Controllable Acceleration and Deceleration of Charge Carrier Transport in Metal-Halide Perovskite Single-Crystal by Cs-Cation Induced Bandgap Engineering.

Charge carrier transport in materials is of essential importance for photovoltaic and photonic applications. Here, the authors demonstrate a controllable acceleration or deceleration of charge carrier transport in specially structured metal-alloy perovskite (MACs)PbI3 (MA= CH3 NH3 ) single-crystals with a gradient composition of CsPbI3 /(MA1- x Csx )PbI3 /MAPbI3 . Depending on the Cs-cation distribution in the structure and therefore the energy band alignment, two different effects are demonstrated: i) significant acceleration of electron transport across the depth driven by the gradient band alignment and suppression of electron-hole recombination, benefiting for photovoltaic and detector applications; and ii) decelerated electron transport and thus improved radiative carrier recombination and emission efficiency, highly beneficial for light and display applications. At the same time, the top Cs-layer results in hole localization in the top layer and surface passivation. This controllable acceleration and deceleration of electron transport is critical for various applications in which efficient electron-hole separation and suppressed nonradiative electron-hole recombination is demanded.

Unique Ultrasonographic Findings of Isolated IgG4-Related Lymphadenopathy.

IgG4-related disease is a rare immune-mediated disease that can involve many organs in the body. The lymph node is also where IgG4-related diseases occur, but its histological structure is different from that of other organs. For this reason, pathologists have difficulty diagnosing IgG4-related lymphadenopathy. If there were specific imaging findings of IgG4-related lymphadenopathy, it would be of great help to pathologists. A 64-year-old male visited our hospital with right ankle pain. On physical examination, the right lower extremity showed severe swelling with wound dehiscence, and infection was suspected. On CT (128-MDCT, Somatom Definition Flash, Siemens Healthcare) taken at the lower extremity, multiple enlarged lymph nodes were incidentally noted in the right inguinal area. On ultrasonography, a "starry night sign" resembling hyperechoic follicles was observed in the enlarged lymph node. A core needle biopsy was performed, and IgG4-related lymphadenopathy was diagnosed. Laboratory examination showed hypergammaglobulinemia with marked elevated serum IgG4, corresponding to IgG4-related disease. Chest and abdominal imaging were evaluated, but there was no extranodal IgG4-related disease. IgG4-related lymphadenopathy showed a very unique ultrasonography imaging finding. The cortex was filled with diffusely scattered hyperechoic foci and some bright foci gathered to form a follicle. This imaging finding may help diagnose IgG4-related lymphadenopathy.

Microstructural Evaluation of Phase Instability in Large Bandgap Metal Halide Perovskites.

The optoelectronic performance of organic-inorganic halide perovskite (OIHP)-based devices has been improved in recent years. Particularly, solar cells fabricated using mixed-cations and mixed-halides have outperformed their single-cation and single-halide counterparts. Yet, a systematic evaluation of the microstructural behavior of mixed perovskites is missing despite their known composition-dependent photoinstability. Here, we explore microstructural inhomogeneity in (FAPbI3)x(MAPbBr3)1-x using advanced scanning probe microscopy techniques. Contact potential difference (CPD) maps measured by Kelvin probe force microscopy show an increased fraction of grains exhibiting a low CPD with flat topography as MAPbBr3 concentration is increased. The higher portion of low CPD contributes to asymmetric CPD distribution curves. Chemical analysis reveals these grains being rich in MA, Pb, and I. The composition-dependent phase segregation upon illumination, reflected on the emergence of a low-energy peak emission in the original photoluminescence spectra, arises from the formation of such grains with flat topology. Bias-dependent piezo-response force microscopy measurements, in these grains, further confirm vigorous ion migration and cause a hysteretic piezo-response. Our results, therefore, provide insights into the microstructural evaluation of phase segregation and ion migration in OIHPs pointing toward process optimization as a mean to further enhance their optoelectronic performance.